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Sample records for sophisticated molecular machines

  1. Engineering molecular machines

    NASA Astrophysics Data System (ADS)

    Erman, Burak

    2016-04-01

    Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

  2. Artificial Molecular Machines.

    PubMed

    Balzani; Credi; Raymo; Stoddart

    2000-10-01

    The miniaturization of components used in the construction of working devices is being pursued currently by the large-downward (top-down) fabrication. This approach, however, which obliges solid-state physicists and electronic engineers to manipulate progressively smaller and smaller pieces of matter, has its intrinsic limitations. An alternative approach is a small-upward (bottom-up) one, starting from the smallest compositions of matter that have distinct shapes and unique properties-namely molecules. In the context of this particular challenge, chemists have been extending the concept of a macroscopic machine to the molecular level. A molecular-level machine can be defined as an assembly of a distinct number of molecular components that are designed to perform machinelike movements (output) as a result of an appropriate external stimulation (input). In common with their macroscopic counterparts, a molecular machine is characterized by 1) the kind of energy input supplied to make it work, 2) the nature of the movements of its component parts, 3) the way in which its operation can be monitored and controlled, 4) the ability to make it repeat its operation in a cyclic fashion, 5) the timescale needed to complete a full cycle of movements, and 6) the purpose of its operation. Undoubtedly, the best energy inputs to make molecular machines work are photons or electrons. Indeed, with appropriately chosen photochemically and electrochemically driven reactions, it is possible to design and synthesize molecular machines that do work. Moreover, the dramatic increase in our fundamental understanding of self-assembly and self-organizational processes in chemical synthesis has aided and abetted the construction of artificial molecular machines through the development of new methods of noncovalent synthesis and the emergence of supramolecular assistance to covalent synthesis as a uniquely powerful synthetic tool. The aim of this review is to present a unified view of the field

  3. Wholly Synthetic Molecular Machines.

    PubMed

    Cheng, Chuyang; Stoddart, J Fraser

    2016-06-17

    The past quarter of a century has witnessed an increasing engagement on the part of physicists and chemists in the design and synthesis of molecular machines de novo. This minireview traces the development of artificial molecular machines from their prototypes in the form of shuttles and switches to their emergence as motors and pumps where supplies of energy in the form of chemical fuel, electrochemical potential and light activation become a minimum requirement for them to function away from equilibrium. The challenge facing this rapidly growing community of scientists and engineers today is one of putting wholly synthetic molecules to work, both individually and as collections. Here, we highlight some of the recent conceptual and practical advances relating to the operation of wholly synthetic rotary and linear motors. PMID:26833859

  4. Fatigue failure and molecular machine design.

    PubMed

    Hess, Henry; Dumont, Emmanuel L P

    2011-06-20

    Sophisticated molecular machines have evolved in nature, and the first synthetic molecular machines have been demonstrated. With our increasing understanding of individual operating cycles, the question of how operation can be sustained over many cycles comes to the forefront. In the design of macroscale machines, performance and lifetime are opposing goals. Similarly, the natural evolution of biological nanomachines, such as myosin motor proteins, is likely constrained by lifetime requirements. Rather than bond rupture at high forces, bond fatigue under repeated small stresses may limit the mechanical performance of molecular machines. Here, the effect of cyclic stresses using single and double bonds as simple examples are discussed. Additionally, it is demonstrated that an increase in lifetime requires a reduction in mechanical load and that molecular engineering design features, such as polyvalent bonds capable of rebinding, can extend the bond lifetime dramatically. A universal scaling law for the force output of motors is extrapolated to the molecular scale to estimate the design space for molecular machines. PMID:21574250

  5. Biological and biomimetic molecular machines.

    PubMed

    Huang, Tony J; Juluri, Bala K

    2008-02-01

    The evolution of life facilitates the creation of biological molecular machines. In these so-called 'nanomachines,' nature elegantly shows that when precisely organized and assembled, simple molecular mechanical components can link motions efficiently from the nanometer scale to the macroscopic world, and achieve complex functions such as powering skeletal muscles, synthesizing ATP and producing DNA/RNA. Inspired by nature, researchers are creating artifical molecular machines with tailored structures and properties, with the aim of realizing man-made active nanosystems that operate with the same efficiency and complexity as biological nanomachines. It is anticipated that in the not-too-distant future, unique applications of biological and biomimetic molecular machines will emerge in areas such as biochemical instrumentation and nanomedicine. PMID:18393670

  6. Controlling Motion at the Nanoscale: Rise of the Molecular Machines.

    PubMed

    Abendroth, John M; Bushuyev, Oleksandr S; Weiss, Paul S; Barrett, Christopher J

    2015-08-25

    As our understanding and control of intra- and intermolecular interactions evolve, ever more complex molecular systems are synthesized and assembled that are capable of performing work or completing sophisticated tasks at the molecular scale. Commonly referred to as molecular machines, these dynamic systems comprise an astonishingly diverse class of motifs and are designed to respond to a plethora of actuation stimuli. In this Review, we outline the conditions that distinguish simple switches and rotors from machines and draw from a variety of fields to highlight some of the most exciting recent examples of opportunities for driven molecular mechanics. Emphasis is placed on the need for controllable and hierarchical assembly of these molecular components to display measurable effects at the micro-, meso-, and macroscales. As in Nature, this strategy will lead to dramatic amplification of the work performed via the collective action of many machines organized in linear chains, on functionalized surfaces, or in three-dimensional assemblies. PMID:26172380

  7. Light-driven artificial molecular machines

    NASA Astrophysics Data System (ADS)

    Zheng, Yue Bing; Hao, Qingzhen; Yang, Ying-Wei; Kiraly, Brian; Chiang, I.-Kao; Huang, Tony Jun

    2010-08-01

    Artificial molecular machines represent a growing field of nanoscience and nanotechnology. Stimulated by chemical reagents, electricity, or light, artificial molecular machines exhibit precisely controlled motion at the molecular level; with this ability molecular machines have the potential to make significant impacts in numerous engineering applications. Compared with molecular machines powered by chemical or electrical energy, light-driven molecular machines have several advantages: light can be switched much faster, work without producing chemical waste, and be used for dual purposes-inducing (writing) as well as detecting (reading) molecular motions. The following issues are significant for light-driven artificial molecular machines in the following aspects: their chemical structures, motion mechanisms, assembly and characterization on solid-state surfaces. Applications in different fields of nanotechnology such as molecular electronics, nano-electro-mechanical systems (NEMS), nanophotonics, and nanomedicine are envisaged.

  8. Molecular machines: Molecules bearing robotic arms

    NASA Astrophysics Data System (ADS)

    Aprahamian, Ivan

    2016-02-01

    Mass production at the nanoscale requires molecular machines that can control, with high fidelity, the spatial orientation of other reactive species. The demonstration of a synthetic system in which a molecular robotic arm can be used to manipulate the position of a chemical cargo is a significant step towards achieving this goal.

  9. "Paper Machine" for Molecular Diagnostics.

    PubMed

    Connelly, John T; Rolland, Jason P; Whitesides, George M

    2015-08-01

    Clinical tests based on primer-initiated amplification of specific nucleic acid sequences achieve high levels of sensitivity and specificity. Despite these desirable characteristics, these tests have not reached their full potential because their complexity and expense limit their usefulness to centralized laboratories. This paper describes a device that integrates sample preparation and loop-mediated isothermal amplification (LAMP) with end point detection using a hand-held UV source and camera phone. The prototype device integrates paper microfluidics (to enable fluid handling) and a multilayer structure, or a "paper machine", that allows a central patterned paper strip to slide in and out of fluidic path and thus allows introduction of sample, wash buffers, amplification master mix, and detection reagents with minimal pipetting, in a hand-held, disposable device intended for point-of-care use in resource-limited environments. This device creates a dynamic seal that prevents evaporation during incubation at 65 °C for 1 h. This interval is sufficient to allow a LAMP reaction for the Escherichia coli malB gene to proceed with an analytical sensitivity of 1 double-stranded DNA target copy. Starting with human plasma spiked with whole, live E. coli cells, this paper demonstrates full integration of sample preparation with LAMP amplification and end point detection with a limit of detection of 5 cells. Further, it shows that the method used to prepare sample enables concentration of DNA from sample volumes commonly available from fingerstick blood draw. PMID:26104869

  10. Mimicking Temperature Through Molecular Machines

    NASA Astrophysics Data System (ADS)

    Smith, David; Käs, Josef

    2003-03-01

    All eukaryotic cells depend on mechanisms of self-assembly of protein filaments to form a cytoskeleton within the cell. The need for motility and reaction by cells to stimuli additionally requires the existence of pathways which serve to restructure and disassemble cytoskeletal structures. Temperature-driven increases in disorder are the most physically fundamental method for breaking down complex structures, yet would play a destructive role in cellular dynamics. A similar situation is seen on the genetic level with the unfolding of DNA strands for replication and cell division - while temperature-driven unfolding of the strands stands as the most simple pathway, molecular machinery are present to perform the same function without heat-induced damage to the cell (Lodish et al, 2000). We report experimental evidence of a similar mechanism functioning on actin cytoskeletal dynamics, involving collections of the actin-specific molecular motor Myosin II. While crosslink-driven bundling self-assembles complex actomyosin structures (including bundles, asters, and large aggregates) in the near-chemical-equilibrum state, an activation of the motors causes a rapid disassembly of all structures. Such a mechanism is not only harmless to cell function, but occurs on a very rapid timescale which is favorable for quick cytoskeletal dynamics.

  11. A Feminist Sophistic?

    ERIC Educational Resources Information Center

    Vitanza, Victor J.

    1995-01-01

    Discusses Susan Jarratt's book "Rereading the Sophists," interrogating her notion of a "feminist sophistic." Discusses the author's own work in terms of a "third sophistic," and calls on writings by Gayatri, Spivak, J. Derrida, and Helene Cixous. (SR)

  12. Light-powered molecular devices and machines.

    PubMed

    Ceroni, Paola; Credi, Alberto; Venturi, Margherita; Balzani, Vincenzo

    2010-12-01

    One century ago Giacomo Ciamician predicted that photochemistry would have had a wealth of useful applications, starting from the conversion of solar energy into fuels. Most of Ciamician's predictions have not yet been achieved, but in the last decade outstanding progress concerning the interaction between light and molecules has led to the creation of artificial photochemical molecular devices and machines capable of using light as an energy supply (to sustain energy-expensive functions) or as an input signal (to be processed and/or stored). This paper illustrates (i) the principles of photochemical molecular devices for information processing, with a few examples of memories, logic functions, and encoding/decoding systems; (ii) the operational mechanisms of light-powered molecular machines, with some examples of rotary motors, shuttles, valves, and switchable boxes; and (iii) the recent progress made in the design and construction of the components of artificial photosynthetic systems. The use of photons to convert abundant low energy molecules into high energy valuable compounds, and to read, write, and erase smart molecular and supramolecular systems for information processing is likely to play a fundamental role for the progress of mankind. PMID:20976372

  13. Fluctuation as a tool of biological molecular machines.

    PubMed

    Yanagida, Toshio

    2008-01-01

    The mechanism for biological molecular machines is different from that of man-made ones. Recently single molecule measurements and other experiments have revealed unique operations where biological molecular machines exploit thermal fluctuation in response to small inputs of energy or signals to achieve their function. Understanding and applying this mechanism to engineering offers new artificial machine designs. PMID:18583025

  14. Molecular machine as chemical-thermodynamic devices

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2013-01-01

    Entropy generation is a fundamental concept in the science of complex systems as well as in engineering applications. The entropy generation approach was developed to obtain the stationary states of these systems. In this Letter, starting from these results, the entropy generation approach is presented as a powerful method useful to analyze molecular machines in relation to their role in living systems. Two examples on cancer are described: (1) the analysis of its evolution which suggests a new approach against it based on entropy generation and (2) the information obtained from the chemical interaction between anticancer drugs and microtubules.

  15. The pulling force of a tiny synthetic molecular machine

    NASA Astrophysics Data System (ADS)

    Svaldo-Lanero, Tiziana; Duwez, Anne-Sophie

    2013-05-01

    In order to function, living organisms use an amazing number of molecular machines. These machines are essential in controlling and performing numerous biological functions, like muscle contraction or intracellular transport. They are able to rectify random thermal motion to generate force and carry out macroscopic tasks. This ability has inspired attempts to create synthetic machines exhibiting control over motion to perform work.

  16. The reducible complexity of a mitochondrial molecular machine

    PubMed Central

    Clements, Abigail; Bursac, Dejan; Gatsos, Xenia; Perry, Andrew J.; Civciristov, Srgjan; Celik, Nermin; Likic, Vladimir A.; Poggio, Sebastian; Jacobs-Wagner, Christine; Strugnell, Richard A.; Lithgow, Trevor

    2009-01-01

    Molecular machines drive essential biological processes, with the component parts of these machines each contributing a partial function or structural element. Mitochondria are organelles of eukaryotic cells, and depend for their biogenesis on a set of molecular machines for protein transport. How these molecular machines evolved is a fundamental question. Mitochondria were derived from an α-proteobacterial endosymbiont, and we identified in α-proteobacteria the component parts of a mitochondrial protein transport machine. In bacteria, the components are found in the inner membrane, topologically equivalent to the mitochondrial proteins. Although the bacterial proteins function in simple assemblies, relatively little mutation would be required to convert them to function as a protein transport machine. This analysis of protein transport provides a blueprint for the evolution of cellular machinery in general. PMID:19717453

  17. The Physics and Physical Chemistry of Molecular Machines.

    PubMed

    Astumian, R Dean; Mukherjee, Shayantani; Warshel, Arieh

    2016-06-17

    The concept of a "power stroke"-a free-energy releasing conformational change-appears in almost every textbook that deals with the molecular details of muscle, the flagellar rotor, and many other biomolecular machines. Here, it is shown by using the constraints of microscopic reversibility that the power stroke model is incorrect as an explanation of how chemical energy is used by a molecular machine to do mechanical work. Instead, chemically driven molecular machines operating under thermodynamic constraints imposed by the reactant and product concentrations in the bulk function as information ratchets in which the directionality and stopping torque or stopping force are controlled entirely by the gating of the chemical reaction that provides the fuel for the machine. The gating of the chemical free energy occurs through chemical state dependent conformational changes of the molecular machine that, in turn, are capable of generating directional mechanical motions. In strong contrast to this general conclusion for molecular machines driven by catalysis of a chemical reaction, a power stroke may be (and often is) an essential component for a molecular machine driven by external modulation of pH or redox potential or by light. This difference between optical and chemical driving properties arises from the fundamental symmetry difference between the physics of optical processes, governed by the Bose-Einstein relations, and the constraints of microscopic reversibility for thermally activated processes. PMID:27149926

  18. Advances Towards Synthetic Machines at the Molecular and Nanoscale Level

    PubMed Central

    Konstas, Kristina; Langford, Steven J.; Latter, Melissa J.

    2010-01-01

    The fabrication of increasingly smaller machines to the nanometer scale can be achieved by either a “top-down” or “bottom-up” approach. While the former is reaching its limits of resolution, the latter is showing promise for the assembly of molecular components, in a comparable approach to natural systems, to produce functioning ensembles in a controlled and predetermined manner. In this review we focus on recent progress in molecular systems that act as molecular machine prototypes such as switches, motors, vehicles and logic operators. PMID:20640163

  19. The Bam machine: A molecular cooper

    PubMed Central

    Ricci, Dante P.; Silhavy, Thomas J.

    2011-01-01

    The bacterial outer membrane (OM) is an exceptional biological structure with a unique composition that contributes significantly to the resiliency of Gram-negative bacteria. Since all OM components are synthesized in the cytosol, the cell must efficiently transport OM-specific lipids and proteins across the cell envelope and stably integrate them into a growing membrane. In this review, we discuss the challenges associated with these processes and detail the elegant solutions that cells have evolved to address the topological problem of OM biogenesis. Special attention will be paid to the Bam machine, a highly conserved multiprotein complex that facilitates OM β-barrel folding. PMID:21893027

  20. Fractal Globules: A New Approach to Artificial Molecular Machines

    PubMed Central

    Avetisov, Vladik A.; Ivanov, Viktor A.; Meshkov, Dmitry A.; Nechaev, Sergei K.

    2014-01-01

    The over-damped relaxation of elastic networks constructed by contact maps of hierarchically folded fractal (crumpled) polymer globules was investigated in detail. It was found that the relaxation dynamics of an anisotropic fractal globule is very similar to the behavior of biological molecular machines like motor proteins. When it is perturbed, the system quickly relaxes to a low-dimensional manifold, M, with a large basin of attraction and then slowly approaches equilibrium, not escaping M. Taking these properties into account, it is suggested that fractal globules, even those made by synthetic polymers, are artificial molecular machines that can transform perturbations into directed quasimechanical motion along a defined path. PMID:25418305

  1. Fractal globules: a new approach to artificial molecular machines.

    PubMed

    Avetisov, Vladik A; Ivanov, Viktor A; Meshkov, Dmitry A; Nechaev, Sergei K

    2014-11-18

    The over-damped relaxation of elastic networks constructed by contact maps of hierarchically folded fractal (crumpled) polymer globules was investigated in detail. It was found that the relaxation dynamics of an anisotropic fractal globule is very similar to the behavior of biological molecular machines like motor proteins. When it is perturbed, the system quickly relaxes to a low-dimensional manifold, M, with a large basin of attraction and then slowly approaches equilibrium, not escaping M. Taking these properties into account, it is suggested that fractal globules, even those made by synthetic polymers, are artificial molecular machines that can transform perturbations into directed quasimechanical motion along a defined path. PMID:25418305

  2. Computational Nanotechnology Molecular Electronics, Materials and Machines

    NASA Technical Reports Server (NTRS)

    Srivastava, Deepak; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    This presentation covers research being performed on computational nanotechnology, carbon nanotubes and fullerenes at the NASA Ames Research Center. Topics cover include: nanomechanics of nanomaterials, nanotubes and composite materials, molecular electronics with nanotube junctions, kinky chemistry, and nanotechnology for solid-state quantum computers using fullerenes.

  3. Physics of molecular machines operated by a particle flux

    NASA Astrophysics Data System (ADS)

    Perez-Carrasco, R.; Sancho, J. M.

    2012-11-01

    Here we present a basic theoretical analysis of molecular machines (turbines) operating with particle fluxes either such as motor or pump regimes. Our focus is on the physical observables: velocity, flux, power and efficiency. We will show that thermal fluctuations are essential to understand its behaviour changing completely the deterministic predictions. Thermal fluctuations introduce a finite domain where no useful output can be extracted from this device due to particle leakage. Furthermore, the maximum of efficiency does not follow the deterministic analysis. Our results also present a bottom line to address the study of these devices in more complex models and to inspire new experiments in this type of machines.

  4. Nietzsche's Reading of the Sophists.

    ERIC Educational Resources Information Center

    Consigny, Scott

    1994-01-01

    Examines Nietzsche's diverse writings on the sophists. Discusses his "genealogical" method of reading in which he situates the sophists as pivotal figures in fifth-century Greece. Examines three features of the sophists' teachings: their rhetorical model of language, their critique of epistemology, and their "immoralism." Discusses a…

  5. Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

    DOE PAGESBeta

    Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O. Anatole; Müller, Klaus -Robert; Tkatchenko, Alexandre

    2015-06-04

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstratemore » prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.« less

  6. Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

    SciTech Connect

    Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O. Anatole; Müller, Klaus -Robert; Tkatchenko, Alexandre

    2015-06-04

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.

  7. Molecular machines operating on the nanoscale: from classical to quantum.

    PubMed

    Goychuk, Igor

    2016-01-01

    The main physical features and operating principles of isothermal nanomachines in the microworld, common to both classical and quantum machines, are reviewed. Special attention is paid to the dual, constructive role of dissipation and thermal fluctuations, the fluctuation-dissipation theorem, heat losses and free energy transduction, thermodynamic efficiency, and thermodynamic efficiency at maximum power. Several basic models are considered and discussed to highlight generic physical features. This work examines some common fallacies that continue to plague the literature. In particular, the erroneous beliefs that one should minimize friction and lower the temperature for high performance of Brownian machines, and that the thermodynamic efficiency at maximum power cannot exceed one-half are discussed. The emerging topic of anomalous molecular motors operating subdiffusively but very efficiently in the viscoelastic environment of living cells is also discussed. PMID:27335728

  8. Application of machine learning to structural molecular biology.

    PubMed

    Sternberg, M J; King, R D; Lewis, R A; Muggleton, S

    1994-06-29

    A technique of machine learning, inductive logic programming implemented in the program GOLEM, has been applied to three problems in structural molecular biology. These problems are: the prediction of protein secondary structure; the identification of rules governing the arrangement of beta-sheets strands in the tertiary folding of proteins; and the modelling of a quantitative structure activity relationship (QSAR) of a series of drugs. For secondary structure prediction and the QSAR, GOLEM yielded predictions comparable with contemporary approaches including neural networks. Rules for beta-strand arrangement are derived and it is planned to contrast their accuracy with those obtained by human inspection. In all three studies GOLEM discovered rules that provided insight into the stereochemistry of the system. We conclude machine learning used together with human intervention will provide a powerful tool to discover patterns in biological sequences and structures. PMID:7800706

  9. Molecular machines operating on the nanoscale: from classical to quantum

    PubMed Central

    2016-01-01

    Summary The main physical features and operating principles of isothermal nanomachines in the microworld, common to both classical and quantum machines, are reviewed. Special attention is paid to the dual, constructive role of dissipation and thermal fluctuations, the fluctuation–dissipation theorem, heat losses and free energy transduction, thermodynamic efficiency, and thermodynamic efficiency at maximum power. Several basic models are considered and discussed to highlight generic physical features. This work examines some common fallacies that continue to plague the literature. In particular, the erroneous beliefs that one should minimize friction and lower the temperature for high performance of Brownian machines, and that the thermodynamic efficiency at maximum power cannot exceed one-half are discussed. The emerging topic of anomalous molecular motors operating subdiffusively but very efficiently in the viscoelastic environment of living cells is also discussed. PMID:27335728

  10. A machine learning approach to computer-aided molecular design.

    PubMed

    Bolis, G; Di Pace, L; Fabrocini, F

    1991-12-01

    Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one--the specialization step--the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase--the generalization step--the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process. PMID:1818094

  11. Artificial Molecular Devices and Machines Driven by Light

    SciTech Connect

    Semeraro, Monica; Silvi, Serena; Credi, Alberto

    2007-12-26

    Light-induced processes are at the basis of fundamental natural phenomena as well as of a variety of applications. Since the functions that can arise from the interaction between light and matter depend on the degree of complexity and organization of the receiving 'matter', the research on these processes has progressively moved from molecular to supramolecular (multicomponent) systems, thereby originating the field of supramolecular photochemistry. In this context, examples of photochemical molecular devices and machines - that is, multicomponent chemical systems capable to perform specific functions under light stimulation - have been developed. Here we describe two recent examples of such systems based on pseudorotaxane and rotaxane species. These studies are of interest not only for the growth of nanoscience, but also for increasing the basic understanding and testing current theoretical treatments of photoinduced processes.

  12. LIFE CYCLE IMPACT ASSESSMENT SOPHISTICATION

    EPA Science Inventory

    An international workshop was held in Brussels on 11/29-30/1998, to discuss LCIA Sophistication. LCA experts from North America, Europs, and Asia attended. Critical reviews of associated factors, including current limitations of available assessment methodologies, and comparison...

  13. The archaeal molecular chaperone machine: peculiarities and paradoxes.

    PubMed Central

    Macario, A J; de Macario, E C

    1999-01-01

    A major finding within the field of archaea and molecular chaperones has been the demonstration that, while some species have the stress (heat-shock) gene hsp70(dnaK), others do not. This gene encodes Hsp70(DnaK), an essential molecular chaperone in bacteria and eukaryotes. Due to the physiological importance and the high degree of conservation of this protein, its absence in archaeal organisms has raised intriguing questions pertaining to the evolution of the chaperone machine as a whole and that of its components in particular, namely, Hsp70(DnaK), Hsp40(DnaJ), and GrpE. Another archaeal paradox is that the proteins coded by these genes are very similar to bacterial homologs, as if the genes had been received via lateral transfer from bacteria, whereas the upstream flanking regions have no bacterial markers, but instead have typical archaeal promoters, which are like those of eukaryotes. Furthermore, the chaperonin system in all archaea studied to the present, including those that possess a bacterial-like chaperone machine, is similar to that of the eukaryotic-cell cytosol. Thus, two chaperoning systems that are designed to interact with a compatible partner, e.g., the bacterial chaperone machine physiologically interacts with the bacterial but not with the eucaryal chaperonins, coexist in archaeal cells in spite of their apparent functional incompatibility. It is difficult to understand how these hybrid characteristics of the archaeal chaperoning system became established and work, if one bears in mind the classical ideas learned from studying bacteria and eukaryotes. No doubt, archaea are intriguing organisms that offer an opportunity to find novel molecules and mechanisms that will, most likely, enhance our understanding of the stress response and the protein folding and refolding processes in the three phylogenetic domains. PMID:10430558

  14. Machine learning of molecular electronic properties in chemical compound space

    NASA Astrophysics Data System (ADS)

    Montavon, Grégoire; Rupp, Matthias; Gobre, Vivekanand; Vazquez-Mayagoitia, Alvaro; Hansen, Katja; Tkatchenko, Alexandre; Müller, Klaus-Robert; Anatole von Lilienfeld, O.

    2013-09-01

    The combination of modern scientific computing with electronic structure theory can lead to an unprecedented amount of data amenable to intelligent data analysis for the identification of meaningful, novel and predictive structure-property relationships. Such relationships enable high-throughput screening for relevant properties in an exponentially growing pool of virtual compounds that are synthetically accessible. Here, we present a machine learning model, trained on a database of ab initio calculation results for thousands of organic molecules, that simultaneously predicts multiple electronic ground- and excited-state properties. The properties include atomization energy, polarizability, frontier orbital eigenvalues, ionization potential, electron affinity and excitation energies. The machine learning model is based on a deep multi-task artificial neural network, exploiting the underlying correlations between various molecular properties. The input is identical to ab initio methods, i.e. nuclear charges and Cartesian coordinates of all atoms. For small organic molecules, the accuracy of such a ‘quantum machine’ is similar, and sometimes superior, to modern quantum-chemical methods—at negligible computational cost.

  15. Implementation of the force decomposition machine for molecular dynamics simulations.

    PubMed

    Borštnik, Urban; Miller, Benjamin T; Brooks, Bernard R; Janežič, Dušanka

    2012-09-01

    We present the design and implementation of the force decomposition machine (FDM), a cluster of personal computers (PCs) that is tailored to running molecular dynamics (MD) simulations using the distributed diagonal force decomposition (DDFD) parallelization method. The cluster interconnect architecture is optimized for the communication pattern of the DDFD method. Our implementation of the FDM relies on standard commodity components even for networking. Although the cluster is meant for DDFD MD simulations, it remains general enough for other parallel computations. An analysis of several MD simulation runs on both the FDM and a standard PC cluster demonstrates that the FDM's interconnect architecture provides a greater performance compared to a more general cluster interconnect. PMID:23085166

  16. Quantifying Changes in Intrinsic Molecular Motion Using Support Vector Machines.

    PubMed

    Leighty, Ralph E; Varma, Sameer

    2013-02-12

    The ensemble of three-dimensional (3-D) configurations exhibited by a molecule, that is, its intrinsic motion, can be altered by several environmental factors, and also by the binding of other molecules. Quantification of such induced changes in intrinsic motion is important because it provides a basis for relating thermodynamic changes to changes in molecular motion. This task is, however, challenging because it requires comparing two high-dimensional data sets. Traditionally, when analyzing molecular simulations, this problem is circumvented by first reducing the dimensions of the two ensembles separately, and then comparing summary statistics from the two ensembles against each other. However, since dimensionality reduction is carried out prior to ensemble comparison, such strategies are susceptible to artifactual biases from information loss. Here, we introduce a method based on support vector machines that yields a normalized quantitative estimate for the difference between two ensembles after comparing them directly against one another. While this method can be applied to any molecular system, including nonbiological molecules and crystals, here, we show how it can be applied to identify the specific regions of a paramyxovirus G protein that are affected by the binding of its preferred human receptor, Ephrin B2. This protein-protein interaction initiates the fusion of the virus with the host cell. Specifically, for every residue in the G protein, we obtain separately a quantitative difference between the ensemble of configurations they sample in the presence and in the absence of Ephrin B2. These ensembles were generated using molecular dynamics simulations. Rank-ordering and then mapping the residues that undergo the greatest change in motion onto the 3-D structure of the G protein reveals that they are clustered primarily on a single contiguous facet of the protein and include the set that is known experimentally to play a vital role in regulating viral

  17. Sophistic Rhetoric: Oasis or Mirage?

    ERIC Educational Resources Information Center

    Schiappa, Edward

    1991-01-01

    Makes the case that sophistic rhetoric is a mirage which vaporizes once carefully scrutinized. Believes that the practice of reproducing incoherent historical concepts is pedagogically unsound, and alternatives should be considered. Suggests specific alternative appropriations that allow educators to retain the best contributions of sophistic…

  18. Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

    PubMed Central

    Chowdhury, Debashish

    2013-01-01

    A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

  19. Ribosomal Dynamics: Intrinsic Instability of a Molecular Machine

    NASA Astrophysics Data System (ADS)

    Gao, Haixiao; Le Barron, Jamie; Frank, Joachim

    Ribosomes are molecular machines that translate genetic message into nascent peptides, through a complex dynamics interplay with mRNAs, tRNAs, and various protein factors. A prominent example of ribosomal dynamics is the rotation of small ribosomal subunit with respect to a large subunit, characterized as the "ratchet motion," which is triggered by the binding of several translation factors. Here, we analyze two kinds of ribosomal ratchet motions, induced by the binding of EF-G and RF3, respectively, as previously observed by cryo-electron microscopy. Using the flexible fitting technique (real-space refinement) and an RNA secondary structure display tool (coloRNA), we obtained quasi-atomic models of the ribosome in these ratchet-motion-related functional states and mapped the observed differences onto the highly conserved RNA secondary structure. Comparisons between two sets of ratchet motions revealed that, while the overall patterns of the RNA displacement are very similar, several local regions stand out in their differential behavior, including the highly conserved GAC (GTPase-associated-center) region. We postulate that these regions are important in modulating general ratchet motion and bestowing it with the dynamic characteristics required for the specific function.

  20. The art and science of self-assembling molecular machines

    NASA Astrophysics Data System (ADS)

    Gómez-López, Marcos; Preece, Jon A.; Fraser Stoddart, J.

    1996-09-01

    In this review, we show how noncovalent bonding interactions between 0957-4484/7/3/004/img1-electron rich aromatic ring systems (e.g. hydroquinone) and the 0957-4484/7/3/004/img1-electron deficient tetracationic cyclophane, cyclobis(paraquat-p-phenylene) can be used to self-assemble novel molecular architectures which are not only interesting to us, because of their fascinating topologies, but also because they have the potential to be developed into molecular structures with switchable properties on the nanometre scale. The high efficiency observed in the self-assembly of a [2]catenane, and its dynamic properties in solution, represent the first step in the design and self-assembly of other molecular assemblies better suited for the study of molecular switching processes. Therefore, a series of [2]rotaxanes, mechanically-interlocked molecular compounds, consisting of a linear 0957-4484/7/3/004/img1-electron rich dumbbell-shaped component and the 0957-4484/7/3/004/img1-electron deficient tetracationic cyclophane as the cyclic component, have been self-assembled and evaluated. All of the so-called molecular shuttles show translational isomerism and one of them, comprising benzidine and biphenol recognition sites as the non-degenerate 0957-4484/7/3/004/img1-electron rich sites, shows molecular switching properties when it is perturbed by external stimuli, such as electrons and protons. The versatility of our approach to nanoscale molecular switches is proven by the description of a series of molecular assemblies and supramolecular arrays, consisting of 0957-4484/7/3/004/img1-electron rich and 0957-4484/7/3/004/img1-electron deficient components, which display molecular switching properties when they are influenced by external stimuli that are photochemical, electrochemical and/or chemical in nature. However, the molecular switching phenomena take place in the solution state. Therefore, finally we describe how simple molecular structures can be ordered on to a solid

  1. Understanding the mechanism of motion in redox-driven molecular machines

    NASA Astrophysics Data System (ADS)

    Share, Andrew Ithan

    New machines open up new opportunities for both creating new devices and investigating new problems. Unlike the engineered machines of the industrial age, recent emphasis in chemistry has focused on making molecular machines that operate on the nanometer length scale. Machines at these scales do not operate like their more familiar macroscopic counterparts, but rather like chemical systems. Most of the prior studies have focused on ensuring that the desired motions between two specific locations occur. Relatively little is known about the mechanism of motion between the two locations. In this Thesis, electroanalytical techniques are used to study the rates and mechanism, i.e., pathways, of motion in redox-controlled molecular machines and their prototypes. The first example of a supramolecular switch that is driven by the reduction of the ligand was discovered. The reduction of bis-bidentate N-heterocyclic ligands provides the driving force for movement of a copper-bound macrocycle between two [2]pseudorotaxanes. Mechanistic studies on this molecular switch revealed that the pathway of motion could be changed when the ligand is reduced. Switching between pathways of motion, e.g., bilability, is expected to play a critical role in the development of unidirectional machines. While the supramolecular pseudorotaxane switches serve as good models for rotaxanes, they do not capture all of the features of molecular machines. Mechanistic studies on a rotaxane that moves a tetracationic ring (cyclobis(paraquat- p-phenylene) between a redox-active tetrathiafulvalene (TTF) and phenylene station were performed. Kinetic studies on the effects of the linker lengths revealed that longer linkers accelerate the ring's movement away from TTF, but slow its return. The mechanistic studies on this rotaxane paved the way for creating an autonomous feedback system to regulate the movements of the rotaxane. Automated, robust and environmentally responsive control schemes are required if

  2. Computational Nanotechnology of Molecular Materials, Electronics and Machines

    NASA Technical Reports Server (NTRS)

    Srivastava, D.; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    This viewgraph presentation covers carbon nanotubes, their characteristics, and their potential future applications. The presentation include predictions on the development of nanostructures and their applications, the thermal characteristics of carbon nanotubes, mechano-chemical effects upon carbon nanotubes, molecular electronics, and models for possible future nanostructure devices. The presentation also proposes a neural model for signal processing.

  3. Crystallographic and chiroptical studies on tetraarylferrocenes for use as chiral rotary modules for molecular machines.

    PubMed

    Muraoka, Takahiro; Kinbara, Kazushi; Wakamiya, Atsushi; Yamaguchi, Shigehiro; Aida, Takuzo

    2007-01-01

    A crystal structure of the racemic form of chiral molecular scissors 1 with a trans configuration at the azobenzene unit (rac-trans-1), in which the scissors adopt a closed geometry with two blade phenyl groups that overlap each other, was successfully determined. X-ray crystallographic determination of the structure of (1S,1'S)-10, which is a derivative of the key precursor of trans-1, was also successful. On the basis of the crystal structure of (1S,1'S)-10, the absolute configuration of 1 and related molecular machines, such as molecular pedal 2, and self-locking rotor 3, which all contain a chiral tetrasubstituted ferrocene module, were determined. A correlation between the absolute configuration and the circular dichroism properties of these molecular machines and their synthetic precursors was also determined. PMID:17146829

  4. Computational approaches to detect allosteric pathways in transmembrane molecular machines.

    PubMed

    Stolzenberg, Sebastian; Michino, Mayako; LeVine, Michael V; Weinstein, Harel; Shi, Lei

    2016-07-01

    Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins, and in particular the recently developed Protein Interaction Analyzer (PIA) designed to study ACNs in the structural ensembles sampled by molecular dynamics simulations. The power of these computational approaches in interrogating the functional mechanisms of transmembrane proteins is illustrated with selected examples of recent experimental and computational studies pursued synergistically in the investigation of secondary active transporters and GPCRs. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID:26806157

  5. Efficient assembly of threaded molecular machines for sequence-specific synthesis.

    PubMed

    De Bo, Guillaume; Kuschel, Sonja; Leigh, David A; Lewandowski, Bartosz; Papmeyer, Marcus; Ward, John W

    2014-04-16

    We report on an improved strategy for the preparation of artificial molecular machines that can pick up and assemble reactive groups in sequence by traveling along a track. In the new approach a preformed rotaxane synthon is attached to the end of an otherwise fully formed strand of building blocks. This "rotaxane-capping" protocol is significantly more efficient than the "final-step-threading" method employed previously and enables the synthesis of threaded molecular machines that operate on extended oligomer, and potentially polymer, tracks. The methodology is exemplified through the preparation of a machine that adds four amino acid building blocks from a strand in sequence, featuring up to 20-membered ring native chemical ligation transition states. PMID:24678971

  6. Identification of a Large SLC25A13 Deletion via Sophisticated Molecular Analyses Using Peripheral Blood Lymphocytes in an Infant with Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency (NICCD): A Clinical and Molecular Study

    PubMed Central

    Zheng, Qi-Qi; Zhang, Zhan-Hui; Zeng, Han-Shi; Lin, Wei-Xia; Yang, Heng-Wen; Yin, Zhi-Nan; Song, Yuan-Zong

    2016-01-01

    Background. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a Mendelian disorder arising from biallelic SLC25A13 mutations, and SLC25A13 genetic analysis was indispensable for its definite diagnosis. However, conventional SLC25A13 analysis could not detect all mutations, especially obscure large insertions/deletions. This paper aimed to explore the obscure SLC25A13 mutation in an NICCD infant. Methods. Genomic DNA was extracted to screen for 4 high-frequency SLC25A13 mutations, and then all 18 exons and their flanking sequences were analyzed by Sanger sequencing. Subsequently, cDNA cloning, SNP analyses, and semiquantitative PCR were performed to identify the obscure mutation. Results. A maternally inherited mutation IVS16ins3kb was screened out, and then cDNA cloning unveiled paternally inherited alternative splicing variants (ASVs) featuring exon 5 skipping. Ultimately, a large deletion c.329-1687_c.468+3865del5692bp, which has never been described in any other references, was identified via intensive study on the genomic DNA around exon 5 of SLC25A13 gene. Conclusions. An NICCD patient was definitely diagnosed as a compound heterozygote of IVS16ins3kb and c.329-1687_c.468+3865del5692bp. The large deletion enriched the SLC25A13 mutation spectrum, and its identification supported the concept that cDNA cloning analysis, along with other molecular tools such as semiquantitative PCR, could provide valuable clues, facilitating the identification of obscure SLC25A13 deletions. PMID:27127784

  7. DNA topology influences molecular machine lifetime in human serum.

    PubMed

    Goltry, Sara; Hallstrom, Natalya; Clark, Tyler; Kuang, Wan; Lee, Jeunghoon; Jorcyk, Cheryl; Knowlton, William B; Yurke, Bernard; Hughes, William L; Graugnard, Elton

    2015-06-21

    DNA nanotechnology holds the potential for enabling new tools for biomedical engineering, including diagnosis, prognosis, and therapeutics. However, applications for DNA devices are thought to be limited by rapid enzymatic degradation in serum and blood. Here, we demonstrate that a key aspect of DNA nanotechnology-programmable molecular shape-plays a substantial role in device lifetimes. These results establish the ability to operate synthetic DNA devices in the presence of endogenous enzymes and challenge the textbook view of near instantaneous degradation. PMID:25959862

  8. DNA topology influences molecular machine lifetime in human serum

    NASA Astrophysics Data System (ADS)

    Goltry, Sara; Hallstrom, Natalya; Clark, Tyler; Kuang, Wan; Lee, Jeunghoon; Jorcyk, Cheryl; Knowlton, William B.; Yurke, Bernard; Hughes, William L.; Graugnard, Elton

    2015-06-01

    DNA nanotechnology holds the potential for enabling new tools for biomedical engineering, including diagnosis, prognosis, and therapeutics. However, applications for DNA devices are thought to be limited by rapid enzymatic degradation in serum and blood. Here, we demonstrate that a key aspect of DNA nanotechnology--programmable molecular shape--plays a substantial role in device lifetimes. These results establish the ability to operate synthetic DNA devices in the presence of endogenous enzymes and challenge the textbook view of near instantaneous degradation.DNA nanotechnology holds the potential for enabling new tools for biomedical engineering, including diagnosis, prognosis, and therapeutics. However, applications for DNA devices are thought to be limited by rapid enzymatic degradation in serum and blood. Here, we demonstrate that a key aspect of DNA nanotechnology--programmable molecular shape--plays a substantial role in device lifetimes. These results establish the ability to operate synthetic DNA devices in the presence of endogenous enzymes and challenge the textbook view of near instantaneous degradation. Electronic supplementary information (ESI) available: DNA sequences, fluorophore and quencher properties, equipment design, and degradation studies. See DOI: 10.1039/c5nr02283e

  9. Spectroscopic studies on chemical- and photo-responsive molecular machines and their bio-applications

    NASA Astrophysics Data System (ADS)

    Lau, Yuen Agnes

    2011-07-01

    The four chapters presented in this dissertation describe how various spectroscopic techniques are used: 1) to study the operation of molecular machines in solution, 2) to track the operation of molecular machines inside a single cell, and 3) to investigate the photo-decomposition pathway of a biological chromophore. Recent advances in nanotechnology have enriched the development of nano-scale molecular assemblies to be used as delivery platforms for biologically relevant molecules. Among all the molecular assemblies, molecular machines that are incorporated onto various domains of mesoporous silica nanoparticles (MSN) hold considerable potential as a reliable delivery system. Because the ease of functionalization enables chemical or photo-responsive molecular moieties to be covalently attached to the silica framework, these molecular assemblies, with defined mechanized properties, can perform specific functions under external stimuli (pH, redox, or light). While the primary function of these molecular machines is to deliver stored cargo molecules, the means of activation and the motif in which they operate are different. In the first and second chapters of this dissertation, two types of molecular machines, nanovalves and nanoimpellers, and their operations are studied. The ability to continuously monitor and image progression of molecular-based biological events in real-time can enhance our understanding of intracellular processes upon drug, protein and nucleic acid delivery. Using the photo-activated nanoimpeller described in the second chapter, the third chapter explores how it can be used to transport a nuclear staining agent, PI, inside a single cell. Nanoimpellers are made by functionalizing azobenzene molecules to the internal pore surface of MSN. The continuous cis/trans isomerizations are set in motion upon laser illumination at optimal wavelength(s), which facilitate cargo molecules to be expelled from the pores to the surrounding medium. By refining a

  10. 70% efficiency of bistate molecular machines explained by information theory, high dimensional geometry and evolutionary convergence

    PubMed Central

    Schneider, Thomas D.

    2010-01-01

    The relationship between information and energy is key to understanding biological systems. We can display the information in DNA sequences specifically bound by proteins by using sequence logos, and we can measure the corresponding binding energy. These can be compared by noting that one of the forms of the second law of thermodynamics defines the minimum energy dissipation required to gain one bit of information. Under the isothermal conditions that molecular machines function this is joules per bit ( is Boltzmann's constant and T is the absolute temperature). Then an efficiency of binding can be computed by dividing the information in a logo by the free energy of binding after it has been converted to bits. The isothermal efficiencies of not only genetic control systems, but also visual pigments are near 70%. From information and coding theory, the theoretical efficiency limit for bistate molecular machines is ln 2 = 0.6931. Evolutionary convergence to maximum efficiency is limited by the constraint that molecular states must be distinct from each other. The result indicates that natural molecular machines operate close to their information processing maximum (the channel capacity), and implies that nanotechnology can attain this goal. PMID:20562221

  11. A Focus on Triazolium as a Multipurpose Molecular Station for pH-Sensitive Interlocked Crown-Ether-Based Molecular Machines

    PubMed Central

    Coutrot, Frédéric

    2015-01-01

    The control of motion of one element with respect to others in an interlocked architecture allows for different co-conformational states of a molecule. This can result in variations of physical or chemical properties. The increase of knowledge in the field of molecular interactions led to the design, the synthesis, and the study of various systems of molecular machinery in a wide range of interlocked architectures. In this field, the discovery of new molecular stations for macrocycles is an attractive way to conceive original molecular machines. In the very recent past, the triazolium moiety proved to interact with crown ethers in interlocked molecules, so that it could be used as an ideal molecular station. It also served as a molecular barrier in order to lock interlaced structures or to compartmentalize interlocked molecular machines. This review describes the recently reported examples of pH-sensitive triazolium-containing molecular machines and their peculiar features. PMID:26491633

  12. A Focus on Triazolium as a Multipurpose Molecular Station for pH-Sensitive Interlocked Crown-Ether-Based Molecular Machines.

    PubMed

    Coutrot, Frédéric

    2015-10-01

    The control of motion of one element with respect to others in an interlocked architecture allows for different co-conformational states of a molecule. This can result in variations of physical or chemical properties. The increase of knowledge in the field of molecular interactions led to the design, the synthesis, and the study of various systems of molecular machinery in a wide range of interlocked architectures. In this field, the discovery of new molecular stations for macrocycles is an attractive way to conceive original molecular machines. In the very recent past, the triazolium moiety proved to interact with crown ethers in interlocked molecules, so that it could be used as an ideal molecular station. It also served as a molecular barrier in order to lock interlaced structures or to compartmentalize interlocked molecular machines. This review describes the recently reported examples of pH-sensitive triazolium-containing molecular machines and their peculiar features. PMID:26491633

  13. Fast and accurate modeling of molecular atomization energies with machine learning.

    PubMed

    Rupp, Matthias; Tkatchenko, Alexandre; Müller, Klaus-Robert; von Lilienfeld, O Anatole

    2012-02-01

    We introduce a machine learning model to predict atomization energies of a diverse set of organic molecules, based on nuclear charges and atomic positions only. The problem of solving the molecular Schrödinger equation is mapped onto a nonlinear statistical regression problem of reduced complexity. Regression models are trained on and compared to atomization energies computed with hybrid density-functional theory. Cross validation over more than seven thousand organic molecules yields a mean absolute error of ∼10  kcal/mol. Applicability is demonstrated for the prediction of molecular atomization potential energy curves. PMID:22400967

  14. Light to investigate (read) and operate (write) molecular devices and machines.

    PubMed

    Ceroni, Paola; Credi, Alberto; Venturi, Margherita

    2014-06-21

    The development of multicomponent (supramolecular) systems that can perform predetermined functions under external control - i.e., molecular devices - is a challenging task in chemistry and a fascinating objective in the frame of a bottom-up approach to nanostructures. In this context light signals can be conveniently used both for supplying energy to the system and for probing its states and transformations. The aim of this tutorial review is to recall a few basic aspects of light-induced processes that can be used to "write" and "read" onto molecular and supramolecular systems. These principles are illustrated through some examples of artificial molecular devices and machines taken from our work, which provide a flavour of current research. They are molecular and supramolecular systems that operate and/or perform valuable functions by exploiting photoinduced energy- or electron-transfer processes, photoisomerization reactions, or photoinduced proton transfer. The choice of these examples was based on both their intrinsic importance for the referred topic and their educational value. In the last section of the review potential applications, limitations and future directions of the research in the field of artificial molecular devices and machines are also discussed. PMID:24590055

  15. DNA-fueled molecular machine for label-free and non-enzymatic ultrasensitive detection of telomerase activity.

    PubMed

    Sun, Panpan; Ran, Xiang; Liu, Chaoqun; Liu, Chaoying; Pu, Fang; Ren, Jinsong; Qu, Xiaogang

    2016-08-01

    Herein, a non-enzymatic and label-free strategy based on DNA-fueled molecular machine was developed for ultrasensitive detection of telomerase activity in cancer cell extracts even at the single-cell level. PMID:27405851

  16. On the Substance of a Sophisticated Epistemology.

    ERIC Educational Resources Information Center

    Elby, Andrew; Hammer, David

    2001-01-01

    Questions the scientific community's consensus on the epistemological sophistication concerning scientific knowledge. Argues for a distinction between correctness and productivity of an epistemological stance and against certain blanket generalizations about the nature of knowledge and learning that do not attend to context. (Author/MM)

  17. How hsp70 molecular machines interact with their substrates to mediate diverse physiological functions.

    PubMed

    Clerico, Eugenia M; Tilitsky, Joseph M; Meng, Wenli; Gierasch, Lila M

    2015-04-10

    Hsp70 molecular chaperones are implicated in a wide variety of cellular processes, including protein biogenesis, protection of the proteome from stress, recovery of proteins from aggregates, facilitation of protein translocation across membranes, and more specialized roles such as disassembly of particular protein complexes. It is a fascinating question to ask how the mechanism of these deceptively simple molecular machines is matched to their roles in these wide-ranging processes. The key is a combination of the nature of the recognition and binding of Hsp70 substrates and the impact of Hsp70 action on their substrates. In many cases, the binding, which relies on interaction with an extended, accessible short hydrophobic sequence, favors more unfolded states of client proteins. The ATP-mediated dissociation of the substrate thus releases it in a relatively less folded state for downstream folding, membrane translocation, or hand-off to another chaperone. There are cases, such as regulation of the heat shock response or disassembly of clathrin coats, however, where binding of a short hydrophobic sequence selects conformational states of clients to favor their productive participation in a subsequent step. This Perspective discusses current understanding of how Hsp70 molecular chaperones recognize and act on their substrates and the relationships between these fundamental processes and the functional roles played by these molecular machines. PMID:25683596

  18. The ligand binding mechanism to purine nucleoside phosphorylase elucidated via molecular dynamics and machine learning

    PubMed Central

    Decherchi, Sergio; Berteotti, Anna; Bottegoni, Giovanni; Rocchia, Walter; Cavalli, Andrea

    2015-01-01

    The study of biomolecular interactions between a drug and its biological target is of paramount importance for the design of novel bioactive compounds. In this paper, we report on the use of molecular dynamics (MD) simulations and machine learning to study the binding mechanism of a transition state analogue (DADMe–immucillin-H) to the purine nucleoside phosphorylase (PNP) enzyme. Microsecond-long MD simulations allow us to observe several binding events, following different dynamical routes and reaching diverse binding configurations. These simulations are used to estimate kinetic and thermodynamic quantities, such as kon and binding free energy, obtaining a good agreement with available experimental data. In addition, we advance a hypothesis for the slow-onset inhibition mechanism of DADMe–immucillin-H against PNP. Combining extensive MD simulations with machine learning algorithms could therefore be a fruitful approach for capturing key aspects of drug–target recognition and binding. PMID:25625196

  19. Recognizing molecular patterns by machine learning: An agnostic structural definition of the hydrogen bond

    SciTech Connect

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-07

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding – a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

  20. Recognizing molecular patterns by machine learning: an agnostic structural definition of the hydrogen bond.

    PubMed

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-01

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding--a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound. PMID:25381505

  1. Recognizing molecular patterns by machine learning: An agnostic structural definition of the hydrogen bond

    NASA Astrophysics Data System (ADS)

    Gasparotto, Piero; Ceriotti, Michele

    2014-11-01

    The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding - a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

  2. On the substance of a sophisticated epistemology

    NASA Astrophysics Data System (ADS)

    Elby, Andrew; Hammer, David

    2001-09-01

    Among researchers who study students' epistemologies, a consensus has emerged about what constitutes a sophisticated stance toward scientific knowledge. According to this community consensus, students should understand scientific knowledge as tentative and evolving, rather than certain and unchanging; subjectively tied to scientists' perspectives, rather than objectively inherent in nature; and individually or socially constructed, rather than discovered. Surveys, interview protocols, and other methods used to probe students' beliefs about scientific knowledge broadly reflect this outlook. This article questions the community consensus about epistemological sophistication. We do not suggest that scientific knowledge is objective and fixed; if forced to choose whether knowledge is certain or tentative, with no opportunity to elaborate, we would choose tentative. Instead, our critique consists of two lines of argument. First, the literature fails to distinguish between the correctness and productivity of an epistemological belief. For instance, elementary school students who believe that science is about discovering objective truths to questions, such as whether the earth is round or flat, or whether an asteroid led to the extinction of the dinosaurs, may be more likely to succeed in science than students who believe science is about telling stories that vary with one's perspective. Naïve realism, although incorrect (according to a broad consensus of philosophers and social scientists), may nonetheless be productive for helping those students learn. Second, according to the consensus view as reflected in commonly used surveys, epistemological sophistication consists of believing certain blanket generalizations about the nature of knowledge and learning, generalizations that do not attend to context. These generalizations are neither correct nor productive. For example, it would be unsophisticated for students to view as tentative the idea that the earth is round

  3. Architecture of the botulinum neurotoxin complex: a molecular machine for protection and delivery

    PubMed Central

    Lam, Kwok-Ho; Jin, Rongsheng

    2015-01-01

    Botulinum neurotoxins (BoNTs) are extremely poisonous protein toxins that cause the fatal paralytic disease botulism. They are naturally produced in bacteria with several nontoxic neurotoxin-associated proteins (NAPs) and together they form a progenitor toxin complex (PTC), the largest bacterial toxin complex known. In foodborne botulism, the PTC functions as a molecular machine that helps BoNT breach the host defense in the gut. Here, we discuss the substantial recent advance in elucidating the atomic structures and assembly of the 14-subunit PTC, including structures of BoNT and four NAPs. These structural studies shed light on the molecular mechanisms by which BoNT is protected against the acidic environment and proteolytic destruction in the gastrointestinal tract, and how it is delivered across the intestinal epithelial barrier. PMID:25889616

  4. Classification of signaling proteins based on molecular star graph descriptors using Machine Learning models.

    PubMed

    Fernandez-Lozano, Carlos; Cuiñas, Rubén F; Seoane, José A; Fernández-Blanco, Enrique; Dorado, Julian; Munteanu, Cristian R

    2015-11-01

    Signaling proteins are an important topic in drug development due to the increased importance of finding fast, accurate and cheap methods to evaluate new molecular targets involved in specific diseases. The complexity of the protein structure hinders the direct association of the signaling activity with the molecular structure. Therefore, the proposed solution involves the use of protein star graphs for the peptide sequence information encoding into specific topological indices calculated with S2SNet tool. The Quantitative Structure-Activity Relationship classification model obtained with Machine Learning techniques is able to predict new signaling peptides. The best classification model is the first signaling prediction model, which is based on eleven descriptors and it was obtained using the Support Vector Machines-Recursive Feature Elimination (SVM-RFE) technique with the Laplacian kernel (RFE-LAP) and an AUROC of 0.961. Testing a set of 3114 proteins of unknown function from the PDB database assessed the prediction performance of the model. Important signaling pathways are presented for three UniprotIDs (34 PDBs) with a signaling prediction greater than 98.0%. PMID:26297890

  5. Computerized materiel management. MMs become increasingly sophisticated.

    PubMed

    Vaughn, J D

    1989-01-01

    The materiel management automation environment is undoubtedly exploding. Hospitals which already rely upon computer systems continue to expand the tasks they perform and department they serve. Even hospitals which have not become reliant upon computers now bring considerable knowledge to the table when negotiating to obtain their first systems. In general, materiel managers continue to grow more sophisticated in hardware and software matters. Most view automation as one the most effective tools they and their hospitals have in controlling expenses. The coming years will surely produce much more system integration as materiel managers begin merging the extensive capabilities of computers with the specific needs and goals of their facilities. PMID:10291639

  6. Irrelevance of the power stroke for the directionality, stopping force, and optimal efficiency of chemically driven molecular machines.

    PubMed

    Astumian, R Dean

    2015-01-20

    A simple model for a chemically driven molecular walker shows that the elastic energy stored by the molecule and released during the conformational change known as the power-stroke (i.e., the free-energy difference between the pre- and post-power-stroke states) is irrelevant for determining the directionality, stopping force, and efficiency of the motor. Further, the apportionment of the dependence on the externally applied force between the forward and reverse rate constants of the power-stroke (or indeed among all rate constants) is irrelevant for determining the directionality, stopping force, and efficiency of the motor. Arguments based on the principle of microscopic reversibility demonstrate that this result is general for all chemically driven molecular machines, and even more broadly that the relative energies of the states of the motor have no role in determining the directionality, stopping force, or optimal efficiency of the machine. Instead, the directionality, stopping force, and optimal efficiency are determined solely by the relative heights of the energy barriers between the states. Molecular recognition--the ability of a molecular machine to discriminate between substrate and product depending on the state of the machine--is far more important for determining the intrinsic directionality and thermodynamics of chemo-mechanical coupling than are the details of the internal mechanical conformational motions of the machine. In contrast to the conclusions for chemical driving, a power-stroke is very important for the directionality and efficiency of light-driven molecular machines and for molecular machines driven by external modulation of thermodynamic parameters. PMID:25606678

  7. Synthetic molecular machines and polymer/monomer size switches that operate through dynamic and non-dynamic covalent changes.

    PubMed

    Stadler, Adrian-Mihail; Ramírez, Juan

    2012-01-01

    The present chapter is focused on how synthetic molecular machines (e.g. shuttles, switches and molecular motors) and size switches (conversions between polymers and their units, i.e., conversions between relatively large and small molecules) can function through covalent changes. Amongst the interesting examples of devices herein presented are molecular motors and size switches based on dynamic covalent chemistry which is an area of constitutional dynamic chemistry. PMID:22169959

  8. Application of Machine Learning tools to recognition of molecular patterns in STM images

    NASA Astrophysics Data System (ADS)

    Maksov, Artem; Ziatdinov, Maxim; Fujii, Shintaro; Kiguchi, Manabu; Higashibayashi, Shuhei; Sakurai, Hidehiro; Kalinin, Sergei; Sumpter, Bobby

    The ability to utilize individual molecules and molecular assemblies as data storage elements has motivated scientist for years, concurrent with the continuous effort to shrink a size of data storage devices in microelectronics industry. One of the critical issues in this effort lies in being able to identify individual molecular assembly units (patterns), on a large scale in an automated fashion of complete information extraction. Here we present a novel method of applying machine learning techniques for extraction of positional and rotational information from scanning tunneling microscopy (STM) images of π-bowl sumanene molecules on gold. We use Markov Random Field (MRF) model to decode the polar rotational states for each molecule in a large scale STM image of molecular film. We further develop an algorithm that uses a convolutional Neural Network combined with MRF and input from density functional theory to classify molecules into different azimuthal rotational classes. Our results demonstrate that a molecular film is partitioned into distinctive azimuthal rotational domains consisting typically of 20-30 molecules. In each domain, the ``bowl-down'' molecules are generally surrounded by six nearest neighbor molecules in ``bowl-up'' configuration, and the resultant overall structure form a periodic lattice of rotational and polar states within each domain. Research was supported by the US Department of Energy.

  9. Irrelevance of the Power Stroke for the Directionality, Stopping Force, and Optimal Efficiency of Chemically Driven Molecular Machines

    PubMed Central

    Astumian, R. Dean

    2015-01-01

    A simple model for a chemically driven molecular walker shows that the elastic energy stored by the molecule and released during the conformational change known as the power-stroke (i.e., the free-energy difference between the pre- and post-power-stroke states) is irrelevant for determining the directionality, stopping force, and efficiency of the motor. Further, the apportionment of the dependence on the externally applied force between the forward and reverse rate constants of the power-stroke (or indeed among all rate constants) is irrelevant for determining the directionality, stopping force, and efficiency of the motor. Arguments based on the principle of microscopic reversibility demonstrate that this result is general for all chemically driven molecular machines, and even more broadly that the relative energies of the states of the motor have no role in determining the directionality, stopping force, or optimal efficiency of the machine. Instead, the directionality, stopping force, and optimal efficiency are determined solely by the relative heights of the energy barriers between the states. Molecular recognition—the ability of a molecular machine to discriminate between substrate and product depending on the state of the machine—is far more important for determining the intrinsic directionality and thermodynamics of chemo-mechanical coupling than are the details of the internal mechanical conformational motions of the machine. In contrast to the conclusions for chemical driving, a power-stroke is very important for the directionality and efficiency of light-driven molecular machines and for molecular machines driven by external modulation of thermodynamic parameters. PMID:25606678

  10. Predicting the auto-ignition temperatures of organic compounds from molecular structure using support vector machine.

    PubMed

    Pan, Yong; Jiang, Juncheng; Wang, Rui; Cao, Hongyin; Cui, Yi

    2009-05-30

    A quantitative structure-property relationship (QSPR) study is suggested for the prediction of auto-ignition temperatures (AIT) of organic compounds. Various kinds of molecular descriptors were calculated to represent the molecular structures of compounds, such as topological, charge, and geometric descriptors. The variable selection method of genetic algorithm (GA) was employed to select optimal subset of descriptors that have significant contribution to the overall AIT property from the large pool of calculated descriptors. The novel modeling method of support vector machine (SVM) was then employed to model the possible quantitative relationship existed between these selected descriptors and AIT property. The resulted model showed high prediction ability with the average absolute error being 28.88 degrees C, and the root mean square error being 36.86 for the prediction set, which are within the range of the experimental error of AIT measurements. The proposed method can be successfully used to predict the auto-ignition temperatures of organic compounds with only nine pre-selected theoretical descriptors which can be calculated directly from molecular structure alone. PMID:18952371

  11. Synthetic Molecular Machines for Active Self-Assembly: Prototype Algorithms, Designs, and Experimental Study

    NASA Astrophysics Data System (ADS)

    Dabby, Nadine L.

    Computer science and electrical engineering have been the great success story of the twentieth century. The neat modularity and mapping of a language onto circuits has led to robots on Mars, desktop computers and smartphones. But these devices are not yet able to do some of the things that life takes for granted: repair a scratch, reproduce, regenerate, or grow exponentially fast--all while remaining functional. This thesis explores and develops algorithms, molecular implementations, and theoretical proofs in the context of "active self-assembly" of molecular systems. The long-term vision of active self-assembly is the theoretical and physical implementation of materials that are composed of reconfigurable units with the programmability and adaptability of biology's numerous molecular machines. En route to this goal, we must first find a way to overcome the memory limitations of molecular systems, and to discover the limits of complexity that can be achieved with individual molecules. One of the main thrusts in molecular programming is to use computer science as a tool for figuring out what can be achieved. While molecular systems that are Turing-complete have been demonstrated [Winfree, 1996], these systems still cannot achieve some of the feats biology has achieved. One might think that because a system is Turing-complete, capable of computing "anything," that it can do any arbitrary task. But while it can simulate any digital computational problem, there are many behaviors that are not "computations" in a classical sense, and cannot be directly implemented. Examples include exponential growth and molecular motion relative to a surface. Passive self-assembly systems cannot implement these behaviors because (a) molecular motion relative to a surface requires a source of fuel that is external to the system, and (b) passive systems are too slow to assemble exponentially-fast-growing structures. We call these behaviors "energetically incomplete" programmable

  12. Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

    PubMed

    Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

    2012-01-01

    Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. PMID:22001671

  13. The tail sheath structure of bacteriophage T4: a molecular machine for infecting bacteria

    SciTech Connect

    Aksyuk, Anastasia A.; Leiman, Petr G.; Kurochkina, Lidia P.; Shneider, Mikhail M.; Kostyuchenko, Victor A.; Mesyanzhinov, Vadim V.; Rossmann, Michael G.

    2009-07-22

    The contractile tail of bacteriophage T4 is a molecular machine that facilitates very high viral infection efficiency. Its major component is a tail sheath, which contracts during infection to less than half of its initial length. The sheath consists of 138 copies of the tail sheath protein, gene product (gp) 18, which surrounds the central non-contractile tail tube. The contraction of the sheath drives the tail tube through the outer membrane, creating a channel for the viral genome delivery. A crystal structure of about three quarters of gp18 has been determined and was fitted into cryo-electron microscopy reconstructions of the tail sheath before and after contraction. It was shown that during contraction, gp18 subunits slide over each other with no apparent change in their structure.

  14. Massive Molecular Outflows Toward Methanol Masers: by Eye and Machine Learning

    NASA Astrophysics Data System (ADS)

    de Villiers, Helena

    2013-07-01

    The best known evolutionary state of massive stars is that of the UC HII region, occurring a few 10^5 years after the initial formation of a massive YSO. Currently objects in the "hot core" phase, occurring prior to the UC HII region, are studied with great interest. Because the YSO is still supposed to be accreting at this stage, one would expect outflows from the central object to develop during this phase, entraining surrounding cold molecular gas in their wake. During this time, 6.7 GHz (Class II) methanol masers will also turn on. They are uniquely associated with massive YSO's, thus serve as a useful signpost. We searched for molecular outflows with the JCMT and HARP focal plane array in a sample of targets toward 6.7 GHz methanol maser coordinates within 20 < Glon < 34. We found 58 CO clumps but only 47 of them were closely associated with the methanol masers. Their spectra were analyzed for broadened line wings, which were found to be present in 46 of the spectra, indicating either bi- or mono-polar outflows. This is a 98% detection frequency. The velocity ranges of these spectrum wings were used to create two dimensional blue and red maps. The out flows' physical parameters were calculated and compared with literature. We created a catalog of kinematic distances and properties of all the 13CO outflows associated with Class II methanol masers, as well as their associated H_2 core and virial masses as derived from the C18O data. In the the light of our results we emphasize the need for an automated detection process, especially with the increasing number of wide-area surveys. We are currently exploring the use of machine learning algorithms (specifically Support Vector Machines) in the detection of high velocity structures in p-p-v cubes.

  15. Multiscale Modeling of Biological Functions: From Enzymes to Molecular Machines (Nobel Lecture)

    PubMed Central

    Warshel, Arieh

    2016-01-01

    Adetailed understanding of the action of biological molecules is a pre-requisite for rational advances in health sciences and related fields. Here, the challenge is to move from available structural information to a clear understanding of the underlying function of the system. In light of the complexity of macromolecular complexes, it is essential to use computer simulations to describe how the molecular forces are related to a given function. However, using a full and reliable quantum mechanical representation of large molecular systems has been practically impossible. The solution to this (and related) problems has emerged from the realization that large systems can be spatially divided into a region where the quantum mechanical description is essential (e.g. a region where bonds are being broken), with the remainder of the system being represented on a simpler level by empirical force fields. This idea has been particularly effective in the development of the combined quantum mechanics/molecular mechanics (QM/MM) models. Here, the coupling between the electrostatic effects of the quantum and classical subsystems has been a key to the advances in describing the functions of enzymes and other biological molecules. The same idea of representing complex systems in different resolutions in both time and length scales has been found to be very useful in modeling the action of complex systems. In such cases, starting with coarse grained (CG) representations that were originally found to be very useful in simulating protein folding, and augmenting them with a focus on electrostatic energies, has led to models that are particularly effective in probing the action of molecular machines. The same multiscale idea is likely to play a major role in modeling of even more complex systems, including cells and collections of cells. PMID:25060243

  16. Ellipsometry: a sophisticated tool for optical metrology

    NASA Astrophysics Data System (ADS)

    Azzam, Rasheed M. A.

    2000-11-01

    Ellipsometry is a sensitive optical technique for non- invasive in-situ (in any optically transparent environment) and ex-situ (in air) characterization of surfaces, interfaces, and thin films which is based on measurement of the polarization of light before and after reflection from a given sample at different angles of incidence and as a function of wavelength. The spectral range of spectroscopic ellipsometry (SE) -typically 1-6eV of photon energy- has been extended to the mid and far IR on one side and to the VUV, EUV, and X-ray region on the other. Significant advances and sophistication of available instrumentation and supportive software have resulted in extensive use of ellipsometry in biology, chemistry, physics, materials science and engineering, and industrial applications over the past two decades. Fast ellipsometers are used for real- time on-line monitoring and feedback process control of various thin films and for the fabrication of pre-engineered multilayer and graded-composition structures. As a metrology tool, ellipsometry yields information on dielectric functions of layered optically isotropic or anisotropic materials, film thicknesses, interface roughnesses, and compositions (void and alloy fractions) and depth profiles of inhomogeneous thin films.

  17. Molecular Bottlebrushes as Tensile Machines for Probing Specific Bonds under Tension

    NASA Astrophysics Data System (ADS)

    Li, Yuanchao; Nese, Alper; Lebedeva, Natalia; Davis, Tyler; Matyjaszewski, Krzysztof; Sheiko, Sergei

    2012-02-01

    Significant tension on the order of 1 nN is self-generated along the backbone of bottlebrush macromolecules due to steric repulsion between densely grafted side chains. The intrinsic tension is amplified upon adsorption of bottlebrush molecules onto a substrate and increases with grafting density, side chain length, and strength of adhesion of the substrate. This allows us to employ these molecular bottlebrushes as miniature tensile machines to probe the mechanochemistry of specific bonds. For this purpose, bottlebrush macromolecules with a disulfide linker in the middle of the backbone were synthesized by atom transfer radical polymerization (ATRP). Two processes, (i) homolytic cleavage of disulfide and (ii) scission of disulfide due to reduction by dithiothreitol were monitored through molecular imaging by atomic force microscope (AFM). In both cases, the corresponding rate constants increase exponentially with mechanical tension along the disulfide bond. Moreover, the reduction rate at zero force is found to be significantly lower than that in bulk solution, which suggests an acidic composition of the water surface with pH=3.7. This opens a new application of brush-like macromolecules as surface pH sensors.

  18. Allosteric Mechanisms of Molecular Machines at the Membrane: Transport by Sodium-Coupled Symporters.

    PubMed

    LeVine, Michael V; Cuendet, Michel A; Khelashvili, George; Weinstein, Harel

    2016-06-01

    Solute transport across cell membranes is ubiquitous in biology as an essential physiological process. Secondary active transporters couple the unfavorable process of solute transport against its concentration gradient to the energetically favorable transport of one or several ions. The study of such transporters over several decades indicates that their function involves complex allosteric mechanisms that are progressively being revealed in atomistic detail. We focus on two well-characterized sodium-coupled symporters: the bacterial amino acid transporter LeuT, which is the prototype for the "gated pore" mechanism in the mammalian synaptic monoamine transporters, and the archaeal GltPh, which is the prototype for the "elevator" mechanism in the mammalian excitatory amino acid transporters. We present the evidence for the role of allostery in the context of a quantitative formalism that can reconcile biochemical and biophysical data and thereby connects directly to recent insights into the molecular structure and dynamics of these proteins. We demonstrate that, while the structures and mechanisms of these transporters are very different, the available data suggest a common role of specific models of allostery in their functions. We argue that such allosteric mechanisms appear essential not only for sodium-coupled symport in general but also for the function of other types of molecular machines in the membrane. PMID:26892914

  19. Hidden Markov models and other machine learning approaches in computational molecular biology

    SciTech Connect

    Baldi, P.

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Computational tools are increasingly needed to process the massive amounts of data, to organize and classify sequences, to detect weak similarities, to separate coding from non-coding regions, and reconstruct the underlying evolutionary history. The fundamental problem in machine learning is the same as in scientific reasoning in general, as well as statistical modeling: to come up with a good model for the data. In this tutorial four classes of models are reviewed. They are: Hidden Markov models; artificial Neural Networks; Belief Networks; and Stochastic Grammars. When dealing with DNA and protein primary sequences, Hidden Markov models are one of the most flexible and powerful alignments and data base searches. In this tutorial, attention is focused on the theory of Hidden Markov Models, and how to apply them to problems in molecular biology.

  20. Synthetic Molecular Machines for Active Self-Assembly: Prototype Algorithms, Designs, and Experimental Study

    NASA Astrophysics Data System (ADS)

    Dabby, Nadine L.

    Computer science and electrical engineering have been the great success story of the twentieth century. The neat modularity and mapping of a language onto circuits has led to robots on Mars, desktop computers and smartphones. But these devices are not yet able to do some of the things that life takes for granted: repair a scratch, reproduce, regenerate, or grow exponentially fast--all while remaining functional. This thesis explores and develops algorithms, molecular implementations, and theoretical proofs in the context of "active self-assembly" of molecular systems. The long-term vision of active self-assembly is the theoretical and physical implementation of materials that are composed of reconfigurable units with the programmability and adaptability of biology's numerous molecular machines. En route to this goal, we must first find a way to overcome the memory limitations of molecular systems, and to discover the limits of complexity that can be achieved with individual molecules. One of the main thrusts in molecular programming is to use computer science as a tool for figuring out what can be achieved. While molecular systems that are Turing-complete have been demonstrated [Winfree, 1996], these systems still cannot achieve some of the feats biology has achieved. One might think that because a system is Turing-complete, capable of computing "anything," that it can do any arbitrary task. But while it can simulate any digital computational problem, there are many behaviors that are not "computations" in a classical sense, and cannot be directly implemented. Examples include exponential growth and molecular motion relative to a surface. Passive self-assembly systems cannot implement these behaviors because (a) molecular motion relative to a surface requires a source of fuel that is external to the system, and (b) passive systems are too slow to assemble exponentially-fast-growing structures. We call these behaviors "energetically incomplete" programmable

  1. Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine

    SciTech Connect

    Mao, D.Y.; Neculai, D.; Downey, M.; Orlicky, S.; Haffani, Y.Z.; Ceccarelli, D.F.; Ho, J.S.; Szilard, R.K.; Zhang, W.; Ho, C.S.; Wan, L.; Fares, C.; Rumpel, S.; Kurinov, I.; Arrowsmith, C.H.; Durocher, D.; Sicheri, F.

    2009-03-27

    Kae1 is a universally conserved ATPase and part of the essential gene set in bacteria. In archaea and eukaryotes, Kae1 is embedded within the protein kinase-containing KEOPS complex. Mutation of KEOPS subunits in yeast leads to striking telomere and transcription defects, but the exact biochemical function of KEOPS is not known. As a first step to elucidating its function, we solved the atomic structure of archaea-derived KEOPS complexes involving Kae1, Bud32, Pcc1, and Cgi121 subunits. Our studies suggest that Kae1 is regulated at two levels by the primordial protein kinase Bud32, which is itself regulated by Cgi121. Moreover, Pcc1 appears to function as a dimerization module, perhaps suggesting that KEOPS may be a processive molecular machine. Lastly, as Bud32 lacks the conventional substrate-recognition infrastructure of eukaryotic protein kinases including an activation segment, Bud32 may provide a glimpse of the evolutionary history of the protein kinase family.

  2. Molecular Machines Regulating the Release Probability of Synaptic Vesicles at the Active Zone.

    PubMed

    Körber, Christoph; Kuner, Thomas

    2016-01-01

    The fusion of synaptic vesicles (SVs) with the plasma membrane of the active zone (AZ) upon arrival of an action potential (AP) at the presynaptic compartment is a tightly regulated probabilistic process crucial for information transfer. The probability of a SV to release its transmitter content in response to an AP, termed release probability (Pr), is highly diverse both at the level of entire synapses and individual SVs at a given synapse. Differences in Pr exist between different types of synapses, between synapses of the same type, synapses originating from the same axon and even between different SV subpopulations within the same presynaptic terminal. The Pr of SVs at the AZ is set by a complex interplay of different presynaptic properties including the availability of release-ready SVs, the location of the SVs relative to the voltage-gated calcium channels (VGCCs) at the AZ, the magnitude of calcium influx upon arrival of the AP, the buffering of calcium ions as well as the identity and sensitivity of the calcium sensor. These properties are not only interconnected, but can also be regulated dynamically to match the requirements of activity patterns mediated by the synapse. Here, we review recent advances in identifying molecules and molecular machines taking part in the determination of vesicular Pr at the AZ. PMID:26973506

  3. Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine

    PubMed Central

    Mao, Daniel Y.L.; Neculai, Dante; Downey, Michael; Orlicky, Stephen; Haffani, Yosr Z.; Ceccarelli, Derek F.; Ho, Jenny S.L.; Szilard, Rachel K.; Zhang, Wei; Ho, Cynthia S.; Wan, Leo; Fares, Christophe; Rumpel, Sigrun; Kurinov, Igor; Arrowsmith, Cheryl H.; Durocher, Daniel; Sicheri, Frank

    2011-01-01

    SUMMARY Kae1 is a universally conserved ATPase and part of the essential gene set in bacteria. In archaea and eukaryotes, Kae1 is embedded within the protein kinase-containing KEOPS complex. Mutation of KEOPS subunits in yeast leads to striking telomere and transcription defects but the exact biochemical function of KEOPS is not known. As a first step to elucidating its function, we solved the atomic structure of archaea-derived KEOPS complexes involving Kae1, Bud32, Pcc1 and Cgi121 subunits. Our studies suggest that Kae1 is regulated at two levels by the primordial protein kinase Bud32, which is itself regulated by Cgi121. Moreover, Pcc1 appears to function as a dimerization module, perhaps suggesting that KEOPS may be a processive molecular machine. Lastly, as Bud32 lacks the conventional substrate-recognition infrastructure of eukaryotic protein kinases including an activation segment, Bud32 may provide a glimpse of the evolutionary history of the protein kinase family. PMID:18951093

  4. Molecular Machines Regulating the Release Probability of Synaptic Vesicles at the Active Zone

    PubMed Central

    Körber, Christoph; Kuner, Thomas

    2016-01-01

    The fusion of synaptic vesicles (SVs) with the plasma membrane of the active zone (AZ) upon arrival of an action potential (AP) at the presynaptic compartment is a tightly regulated probabilistic process crucial for information transfer. The probability of a SV to release its transmitter content in response to an AP, termed release probability (Pr), is highly diverse both at the level of entire synapses and individual SVs at a given synapse. Differences in Pr exist between different types of synapses, between synapses of the same type, synapses originating from the same axon and even between different SV subpopulations within the same presynaptic terminal. The Pr of SVs at the AZ is set by a complex interplay of different presynaptic properties including the availability of release-ready SVs, the location of the SVs relative to the voltage-gated calcium channels (VGCCs) at the AZ, the magnitude of calcium influx upon arrival of the AP, the buffering of calcium ions as well as the identity and sensitivity of the calcium sensor. These properties are not only interconnected, but can also be regulated dynamically to match the requirements of activity patterns mediated by the synapse. Here, we review recent advances in identifying molecules and molecular machines taking part in the determination of vesicular Pr at the AZ. PMID:26973506

  5. Characteristics and Levels of Sophistication: An Analysis of Chemistry Students' Ability to Think with Mental Models

    ERIC Educational Resources Information Center

    Wang, Chia-Yu; Barrow, Lloyd H.

    2011-01-01

    This study employed a case-study approach to reveal how an ability to think with mental models contributes to differences in students' understanding of molecular geometry and polarity. We were interested in characterizing features and levels of sophistication regarding first-year university chemistry learners' mental modeling behaviors while the…

  6. Definition and Measurement of End User Computing Sophistication.

    ERIC Educational Resources Information Center

    Blili, Samir; And Others

    1996-01-01

    To conceptualize and measure end user computing sophistication, a three-dimensional characterization of application, usage, and end user sophistication is proposed. A preliminary operationalization using 9 variables was tested with 505 users in 5 Canadian enterprises and found to be globally reliable. Contains five tables and an appendix which…

  7. Automatically Assessing Lexical Sophistication: Indices, Tools, Findings, and Application

    ERIC Educational Resources Information Center

    Kyle, Kristopher; Crossley, Scott A.

    2015-01-01

    This study explores the construct of lexical sophistication and its applications for measuring second language lexical and speaking proficiency. In doing so, the study introduces the Tool for the Automatic Analysis of LExical Sophistication (TAALES), which calculates text scores for 135 classic and newly developed lexical indices related to word…

  8. The Impact of Financial Sophistication on Adjustable Rate Mortgage Ownership

    ERIC Educational Resources Information Center

    Smith, Hyrum; Finke, Michael S.; Huston, Sandra J.

    2011-01-01

    The influence of a financial sophistication scale on adjustable-rate mortgage (ARM) borrowing is explored. Descriptive statistics and regression analysis using recent data from the Survey of Consumer Finances reveal that ARM borrowing is driven by both the least and most financially sophisticated households but for different reasons. Less…

  9. A compact, dual-stage actuator with displacement sensors for the molecular measuring machine

    NASA Astrophysics Data System (ADS)

    Li, Jing

    In this dissertation, we present the design, modification, optimization, assembly, performance characterization, calibration, and uncertainty analysis for a compact, for the Molecular Measuring Machine (M3) at the National Institute of Standards and Technology. The 3 is a scanning probe microscope (SPM) designed for making measurements with nanometer-level uncertainty over a working area of 50 mm by 50 mm. The design of the Z-motion assembly is a particular challenge due to various constraints, especially a limited available volume of 25 mm in height and 35 mm in diameter, and the need for repeatable motion generation with integrated high resolution sensors. In the ultra limited space, the Z-motion assembly is composed a coarse-motion stage and a fine-motion stage. The coarse-motion stage is a piezoceramic inchworm-like stepping motor with a potentiometer-type position sensor. It is capable of translating the probe over a 3 mm range with overshoot-free steps ranging from 1 microm to 2 microm. The fine-motion stage is a flexure-guided, piezoceramic-driven actuator to generate high-speed motion with a linear differential capacitive position sensor. A flexure-hinge drive plate is designed as a motion amplifier to keep the stroke of the fine-motion actuator at more than 8 microm. An analytical solution is developed and optimization routines are used to optimize the design of the drive plate. The calculated deformations of the flexure amplifier show good agreement with experimental results. A differential capacitance gauge with high signal-to-noise ratio AC bridge is designed as the fine-motion position sensor, which has noise floor better than 0.1 nm. To validate the performance and calibration, a series of step-height gratings with step heights ranging from 84 nm to 1.5 microm are measured using the Z-motion assembly and compared with the calibration results from NIST. The uncertainty budgets for measurements made with the Z-motion assembly are evaluated and found to

  10. Carbon sequestration in Synechococcus Sp.: from molecular machines to hierarchical modeling.

    SciTech Connect

    Martino, Anthony A. (Sandia National Laboratories, Livermore, CA); Heffelfinger, Grant S.; Frink, Laura J. Douglas; Davidson, George S.; Haaland, David Michael; Timlin, Jerilyn Ann; Plimpton, Steven James; Lane, Todd W.; Thomas, Edward Victor; Rintoul, Mark Daniel; Roe, Diana C. (Sandia National Laboratories, Livermore, CA); Faulon, Jean-Loup Michel; Hart, William Eugene

    2003-02-01

    The U.S. Department of Energy recently announced the first five grants for the Genomes to Life (GTL) Program. The goal of this program is to ''achieve the most far-reaching of all biological goals: a fundamental, comprehensive, and systematic understanding of life.'' While more information about the program can be found at the GTL website (www.doegenomestolife.org), this paper provides an overview of one of the five GTL projects funded, ''Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling.'' This project is a combined experimental and computational effort emphasizing developing, prototyping, and applying new computational tools and methods to elucidate the biochemical mechanisms of the carbon sequestration of Synechococcus Sp., an abundant marine cyanobacteria known to play an important role in the global carbon cycle. Understanding, predicting, and perhaps manipulating carbon fixation in the oceans has long been a major focus of biological oceanography and has more recently been of interest to a broader audience of scientists and policy makers. It is clear that the oceanic sinks and sources of CO(2) are important terms in the global environmental response to anthropogenic atmospheric inputs of CO(2) and that oceanic microorganisms play a key role in this response. However, the relationship between this global phenomenon and the biochemical mechanisms of carbon fixation in these microorganisms is poorly understood. The project includes five subprojects: an experimental investigation, three computational biology efforts, and a fifth which deals with addressing computational infrastructure challenges of relevance to this project and the Genomes to Life program as a whole. Our experimental effort is designed to provide biology and data to drive the computational efforts and includes significant investment in developing new experimental methods for uncovering protein partners, characterizing protein complexes, identifying new

  11. Mechanoelectrical and Photon-Generating Devices in Cells and Organisms: From Molecular Machines to Macroscopic Fields

    NASA Astrophysics Data System (ADS)

    Beloussov, L. V.

    2011-12-01

    The aim of this essay is to review what we know about the transformation of chemical energy into mechanical, electrical and photonic at the different scales of biological organization. We start from the "classical", short-range mechanoelectrical protein machines emphasizing their capacity to slow down the rate of energy relaxation and to concentrate energy onto a restricted number of freedom degrees. Then we pass to the newly described "low entropy machines" and to the macroscopic electromechanical machines which create circuits of the organismal scales. At last, we come to photonic events, paying a special attention to their regular periodicity within several Hz range and to their relations with cytoskeletal structures and their developmental dynamics. We suggest, that this area of investigations should be related with the theory of self-organization and the notion of coherency.

  12. Just Working with the Cellular Machine: A High School Game for Teaching Molecular Biology

    ERIC Educational Resources Information Center

    Cardoso, Fernanda Serpa; Dumpel, Renata; Gomes da Silva, Luisa B.; Rodrigues, Carlos R.; Santos, Dilvani O.; Cabral, Lucio Mendes; Castro, Helena C.

    2008-01-01

    Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several…

  13. An information-carrying and knowledge-producing molecular machine. A Monte-Carlo simulation.

    PubMed

    Kuhn, Christoph

    2012-02-01

    The concept called Knowledge is a measure of the quality of genetically transferred information. Its usefulness is demonstrated quantitatively in a Monte-Carlo simulation on critical steps in a origin of life model. The model describes the origin of a bio-like genetic apparatus by a long sequence of physical-chemical steps: it starts with the presence of a self-replicating oligomer and a specifically structured environment in time and space that allow for the formation of aggregates such as assembler-hairpins-devices and, at a later stage, an assembler-hairpins-enzyme device-a first translation machine. PMID:21559961

  14. Modeling the adsorption of PAH mixture in silica nanopores by molecular dynamic simulation combined with machine learning.

    PubMed

    Sui, Hong; Li, Lin; Zhu, Xinzhe; Chen, Daoyi; Wu, Guozhong

    2016-02-01

    The persistence of polycyclic aromatic hydrocarbons (PAHs) in contaminated soils is largely controlled by their molecular fate in soil pores. The adsorption and diffusion of 16 PAHs mixture in silica nanopore with diameter of 2.0, 2.5, 3.0 and 3.5 nm, respectively, were characterized by adsorption energy, mean square displacement, free surface area and free volume fraction using molecular dynamic (MD) simulation. Results suggested that PAHs adsorption in silica nanopores was associated with diffusion process while competitive sorption was not the dominant mechanism in context of this study. The partial least squares (PLS) regression and machine learning (ML) methods (i.e. support vector regression, M5 decision tree and multilayer perceptrons) were used to correlate the adsorption energy with the pore diameter and PAH properties (number of carbon atoms, aromatic ring number, boiling point, molecular weight, octanol-water partition coefficient, octanol-organic carbon partition coefficient, solvent accessible area, solvent accessible volume and polarization). Results indicated that the PAH adsorption could not be predicted by linear regression as the R(2)Y and Q(2)Y coefficients of PLS analysis was 0.375 and 0.199, respectively. The nonlinearity was well recognized by ML with correlation coefficient up to 0.9. Overall, the combination of MD simulation and ML approaches can assist in interpreting the sequestration of organic contaminants in the soil nanopores. PMID:26547031

  15. Identification of Glucose-Binding Pockets in Human Serum Albumin Using Support Vector Machine and Molecular Dynamics Simulations.

    PubMed

    Ranganarayanan, Preethi; Thanigesan, Narmadha; Ananth, Vivek; Jayaraman, Valadi K; Ramakrishnan, Vigneshwar

    2016-01-01

    Human Serum Albumin (HSA) has been suggested to be an alternate biomarker to the existing Hemoglobin-A1c (HbA1c) marker for glycemic monitoring. Development and usage of HSA as an alternate biomarker requires the identification of glycation sites, or equivalently, glucose-binding pockets. In this work, we combine molecular dynamics simulations of HSA and the state-of-art machine learning method Support Vector Machine (SVM) to predict glucose-binding pockets in HSA. SVM uses the three dimensional arrangement of atoms and their chemical properties to predict glucose-binding ability of a pocket. Feature selection reveals that the arrangement of atoms and their chemical properties within the first 4Å from the centroid of the pocket play an important role in the binding of glucose. With a 10-fold cross validation accuracy of 84 percent, our SVM model reveals seven new potential glucose-binding sites in HSA of which two are exposed only during the dynamics of HSA. The predictions are further corroborated using docking studies. These findings can complement studies directed towards the development of HSA as an alternate biomarker for glycemic monitoring. PMID:26886739

  16. An Interaction Network Predicted from Public Data as a Discovery Tool: Application to the Hsp90 Molecular Chaperone Machine

    PubMed Central

    Echeverría, Pablo C.; Bernthaler, Andreas; Dupuis, Pierre; Mayer, Bernd; Picard, Didier

    2011-01-01

    Understanding the functions of proteins requires information about their protein-protein interactions (PPI). The collective effort of the scientific community generates far more data on any given protein than individual experimental approaches. The latter are often too limited to reveal an interactome comprehensively. We developed a workflow for parallel mining of all major PPI databases, containing data from several model organisms, and to integrate data from the literature for a protein of interest. We applied this novel approach to build the PPI network of the human Hsp90 molecular chaperone machine (Hsp90Int) for which previous efforts have yielded limited and poorly overlapping sets of interactors. We demonstrate the power of the Hsp90Int database as a discovery tool by validating the prediction that the Hsp90 co-chaperone Aha1 is involved in nucleocytoplasmic transport. Thus, we both describe how to build a custom database and introduce a powerful new resource for the scientific community. PMID:22022502

  17. AN INTERNATIONAL WORKSHOP ON LIFE CYCLE IMPACT ASSESSMENT SOPHISTICATION

    EPA Science Inventory

    On November 29-30,1998 in Brussels, an international workshop was held to discuss Life Cycle Impact Assessment (LCIA) Sophistication. Approximately 50 LCA experts attended the workshop from North America, Europe, and Asia. Prominant practicioners and researchers were invited to p...

  18. Naive vs. Sophisticated Methods of Forecasting Public Library Circulations.

    ERIC Educational Resources Information Center

    Brooks, Terrence A.

    1984-01-01

    Two sophisticated--autoregressive integrated moving average (ARIMA), straight-line regression--and two naive--simple average, monthly average--forecasting techniques were used to forecast monthly circulation totals of 34 public libraries. Comparisons of forecasts and actual totals revealed that ARIMA and monthly average methods had smallest mean…

  19. Antecedents of clinical information technology sophistication in hospitals.

    PubMed

    Jaana, Mirou; Ward, Marcia M; Paré, Guy; Sicotte, Claude

    2006-01-01

    Grounded in the resource-based theory and the innovation diffusion theory, this article develops and tests a research model for assessing the antecedents of hospital innovativeness with regard to clinical information technology (IT) applications. A cross-sectional survey was conducted in a sample of U.S. hospitals (n = 74) to assess three dimensions of clinical IT sophistication. Secondary data were used to measure the antecedents, namely, four groups of organizational capacity variables. Bivariate and regression analyses were conducted to identify significant associations. A significant percentage (45-61%) of the variance in clinical IT sophistication was explained, mostly by leadership and knowledge sharing capacities. In particular, IT tenure and technical knowledge resources were significantly related to clinical IT sophistication. Surprisingly, managerial tenure and hospital's belonging to a network showed significant negative associations with two dimensions of the clinical IT sophistication construct. To address the challenges they face, hospitals should consider encouraging career development for current individuals in charge of IT activities, and attracting professionals with an IT background who have the knowledge and ability to trigger new ideas and favor the adoption and use of clinical IT applications in these settings. PMID:17077703

  20. Bodily Pedagogies: Rhetoric, Athletics, and the Sophists' Three Rs.

    ERIC Educational Resources Information Center

    Hawhee, Debra

    2002-01-01

    Explores a connection that inhered in ancient practices, a connection not as apparently relevant to contemporary pedagogy, but just might be: that between rhetorical training and athletic training. Looks at two considerations that help render more salient the cultural and historical connections. Discusses how the sophists emphasized the…

  1. AN INTERNATIONAL WORKSHOP ON LIFE CYCLE IMPACT ASSESSMENT SOPHISTICATION

    EPA Science Inventory

    On November 29-30,1998 in Brussels, an international workshop was held to discuss Life Cycle Impact Assessment (LCIA) Sophistication. Approximately 50 LCA experts attended the workshop from North America, Europe, and Asia. Prominant practicioners and researchers were invited to ...

  2. The Feminist Sophistic Enterprise: From Euripides to the Vietnam War.

    ERIC Educational Resources Information Center

    Wick, Audrey

    1992-01-01

    Uses feminist sophistic historiography to open the doors of two distant historical movements onto each other, reading tensions between masculinity and femininity in Athens during the Peloponnesian war and in the United States during the Vietnam War. Foregrounds the possibility of forestalling arbitrary closure on gender questions which determined…

  3. Issues on machine learning for prediction of classes among molecular sequences of plants and animals

    NASA Astrophysics Data System (ADS)

    Stehlik, Milan; Pant, Bhasker; Pant, Kumud; Pardasani, K. R.

    2012-09-01

    Nowadays major laboratories of the world are turning towards in-silico experimentation due to their ease, reproducibility and accuracy. The ethical issues concerning wet lab experimentations are also minimal in in-silico experimentations. But before we turn fully towards dry lab simulations it is necessary to understand the discrepancies and bottle necks involved with dry lab experimentations. It is necessary before reporting any result using dry lab simulations to perform in-depth statistical analysis of the data. Keeping same in mind here we are presenting a collaborative effort to correlate findings and results of various machine learning algorithms and checking underlying regressions and mutual dependencies so as to develop an optimal classifier and predictors.

  4. Just working with the cellular machine: A high school game for teaching molecular biology.

    PubMed

    Cardoso, Fernanda Serpa; Dumpel, Renata; da Silva, Luisa B Gomes; Rodrigues, Carlos R; Santos, Dilvani O; Cabral, Lucio Mendes; Castro, Helena C

    2008-03-01

    Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several questions and a game story that invites the students for helping the human immunological system to produce antibodies (IgG) and fight back a pathogenic bacterium second-time invasion. The game involves answering questions completing the game board in which the antibodies "are synthesized" through the molecular biology process. At the end, a problem-based learning approach is used, and a last question is raised about proteins. Biology teachers and high school students evaluated the game and considered it an easy and interesting tool for teaching the theme. An increase of about 5-30% in answering molecular biology questions revealed that the game improves learning and induced a more engaged and proactive learning profile in the high school students. PMID:21591175

  5. Active Esters as Pseudostoppers for Slippage Synthesis of [2]Pseudorotaxane Building Blocks: A Straightforward Route to Multi-Interlocked Molecular Machines.

    PubMed

    Legigan, Thibaut; Riss-Yaw, Benjamin; Clavel, Caroline; Coutrot, Frédéric

    2016-06-20

    The efficient synthesis and very easy isolation of dibenzo[24]crown-8-based [2]pseudorotaxane building blocks that contain an active ester motif at the extremity of the encircled molecular axle and an ammonium moiety as a template for the dibenzo[24]crown-8 is reported. The active ester acts both as a semistopper for the [2]pseudorotaxane species and as an extensible extremity. Among the various investigated active ester moieties, those that allow for the slippage process are given particular focus because this strategy produces fewer side products. Extension of the selected N-hydroxysuccinimide ester based pseudorotaxane building block by using either a mono- or a diamino compound, both containing a triazolium moiety, is also described. These provide a pH-dependent two-station [2]rotaxane molecular machine and a palindromic [3]rotaxane molecular machine, respectively. Molecular machinery on both interlocked compounds through variation of pH was studied and characterized by means of NMR spectroscopy. PMID:27239975

  6. A State Profile of IT Sophistication in Nursing Homes

    PubMed Central

    Alexander, Gregory L.

    2008-01-01

    In healthcare, IT sophistication has been defined as the diversity and maturity of information system hardware and software that support clinical services. Clinical services relevant to this study include resident care management, clinical support and administrative activities in nursing homes. An IT sophistication survey previously validated in acute care settings and adapted for nursing homes was used to develop a state profile of Missouri nursing homes. The IT survey was disseminated via paper and electronic methods as chosen by a selected responder that had IT oversight and knowledge of IT stakeholders. A census of 199 respondents completed the survey, representing a 41% (199/491) response rate. Findings support recent literature indicating a higher percentage of nursing homes are still using technology for administrative purposes; however, there is growing recognition that technologies with greater functionality, is used more extensively for electronic and automated transfer of resident care information. PMID:18999316

  7. Biologically inspired, sophisticated motions from helically assembled, conducting fibers.

    PubMed

    Chen, Peining; Xu, Yifan; He, Sisi; Sun, Xuemei; Guo, Wenhan; Zhang, Zhitao; Qiu, Longbin; Li, Jianfeng; Chen, Daoyong; Peng, Huisheng

    2015-02-11

    A hierarchically helical organization of carbon nanotubes into macroscopic fibers enables sophistication while controlling three-dimensional electromechanical actuations, e.g., an artificial swing and tail. The actuation generates a stress of more than 260 times that of a typical natural skeletal muscle and an accelerated velocity of more than 10 times that of a cheetah at low electric currents with high reversibility, good stability, and availability to various media. PMID:25446835

  8. Tubulin-specific Chaperones: Components of a Molecular Machine that Assembles the α/β Heterodimer

    PubMed Central

    Tian, Guoling; Cowan, Nicholas J.

    2016-01-01

    The tubulin heterodimer consists of one α- and one β-tubulin polypeptide. Neither protein can partition to the native state or assemble into polymerization competent heterodimers without the concerted action of a series of chaperone proteins including five tubulin-specific chaperones termed TBCA-TBCE. TBCA and TBCB bind to and stabilize newly synthesized quasi-native β- and α-tubulin polypeptides following their generation via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin, CCT. There is free exchange β-tubulin between TBCA and TBCD, and of α-tubulin between TBCB and TBCE, resulting in the formation of TBCD/β and TBCE/α, respectively. The latter two complexes interact, forming a supercomplex (TBCD/α/TBCD/β). Discharge of the native α/β heterodimer occurs via interaction of the supercomplex with TBCC, which results in the triggering of TBC-bound β-tubulin-bound (E-site) GTP hydrolysis. This reaction acts as a switch for disassembly of the supercomplex and the release of GDP-bound heterodimer, which becomes polymerization competent following spontaneous E-site exchange with GTP. The tubulin-specific chaperones thus function together as a tubulin assembly machine, marrying the α- and β-tubulin subunits into a tightly associated heterodimer. The existence of this evolutionarily conserved pathway explains why it has never proved possible to isolate α- or β-tubulin as stable independent entities in the absence of their cognate partners, and implies that each exists and is maintained in the heterodimer in a non-minimal energy state. Here we describe methods for the purification of recombinant TBC’s as biologically active proteins following their expression in a variety of host/vector systems. PMID:23973072

  9. Molecular Machines Determining the Fate of Endocytosed Synaptic Vesicles in Nerve Terminals

    PubMed Central

    Fassio, Anna; Fadda, Manuela; Benfenati, Fabio

    2016-01-01

    The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission. PMID:27242505

  10. Molecular Machines Determining the Fate of Endocytosed Synaptic Vesicles in Nerve Terminals.

    PubMed

    Fassio, Anna; Fadda, Manuela; Benfenati, Fabio

    2016-01-01

    The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission. PMID:27242505

  11. Induction of motion in a synthetic molecular machine: effect of tuning the driving force.

    PubMed

    Baggerman, Jacob; Haraszkiewicz, Natalia; Wiering, Piet G; Fioravanti, Giulia; Marcaccio, Massimo; Paolucci, Francesco; Kay, Euan R; Leigh, David A; Brouwer, Albert M

    2013-04-26

    Rotaxane molecular shuttles were studied in which a tetralactam macrocyclic ring moves between a succinamide station and a second station in which the structure is varied. Station 2 in all cases is an aromatic imide, which is a poor hydrogen-bond acceptor in the neutral form, but a strong one when reduced with one or two electrons. When the charge density on the hydrogen-bond-accepting carbonyl groups in station 2 is reduced by changing a naphthalimide into a naphthalene diimide radical anion, the shuttling rate changes only slightly. When station 2 is a pyromellitimide radical anion, however, the shuttling rate is significantly reduced. This implies that the shuttling rate is not only determined by the initial unbinding of the ring from the first station, as previously supposed. An alternative reaction mechanism is proposed in which the ring binds to both stations in the transition state. PMID:23564495

  12. Rotation of a bulky triptycene in the solid state: toward engineered nanoscale artificial molecular machines.

    PubMed

    Jiang, Xing; Rodríguez-Molina, Braulio; Nazarian, Narega; Garcia-Garibay, Miguel A

    2014-06-25

    We report the design and dynamics of a solid-state molecular rotor with a large triptycene rotator. With a cross-section and surface area that are 2 and 3 times larger than those of the phenylene rotators previously studied in the solid state, it is expected that van der Waals forces and steric hindrance will render the motion of the larger triptycene more difficult. To address this challenge, we used a rigid and shape-persistent stator in a dendritic structure that reaches ca. 3.6 nm in length. Using variable-temperature solid-state (2)H NMR spectroscopy, we determined a symmetric three-fold rotational potential with a barrier of 10.2 kcal/mol and a pre-exponential factor of 1.1 × 10(10) s(-1), which correspond to ca. 4600 Brownian jumps per second in the solid state at 300 K. PMID:24911467

  13. Fast plane wave density functional theory molecular dynamics calculations on multi-GPU machines

    SciTech Connect

    Jia, Weile; University of Chinese Academy of Sciences, Beijing ; Fu, Jiyun; University of Chinese Academy of Sciences, Beijing ; Cao, Zongyan; Wang, Long; Chi, Xuebin; Gao, Weiguo; MOE Key Laboratory of Computational Physical Sciences, Fudan University, Shanghai ; Wang, Lin-Wang

    2013-10-15

    Plane wave pseudopotential (PWP) density functional theory (DFT) calculation is the most widely used method for material simulations, but its absolute speed stagnated due to the inability to use large scale CPU based computers. By a drastic redesign of the algorithm, and moving all the major computation parts into GPU, we have reached a speed of 12 s per molecular dynamics (MD) step for a 512 atom system using 256 GPU cards. This is about 20 times faster than the CPU version of the code regardless of the number of CPU cores used. Our tests and analysis on different GPU platforms and configurations shed lights on the optimal GPU deployments for PWP-DFT calculations. An 1800 step MD simulation is used to study the liquid phase properties of GaInP.

  14. Protein-protein interaction networks: unraveling the wiring of molecular machines within the cell.

    PubMed

    De Las Rivas, Javier; Fontanillo, Celia

    2012-11-01

    Mapping and understanding of the protein interaction networks with their key modules and hubs can provide deeper insights into the molecular machinery underlying complex phenotypes. In this article, we present the basic characteristics and definitions of protein networks, starting with a distinction of the different types of associations between proteins. We focus the review on protein-protein interactions (PPIs), a subset of associations defined as physical contacts between proteins that occur by selective molecular docking in a particular biological context. We present such definition as opposed to other types of protein associations derived from regulatory, genetic, structural or functional relations. To determine PPIs, a variety of binary and co-complex methods exist; however, not all the technologies provide the same information and data quality. A way of increasing confidence in a given protein interaction is to integrate orthogonal experimental evidences. The use of several complementary methods testing each single interaction assesses the accuracy of PPI data and tries to minimize the occurrence of false interactions. Following this approach there have been important efforts to unify primary databases of experimentally proven PPIs into integrated databases. These meta-databases provide a measure of the confidence of interactions based on the number of experimental proofs that report them. As a conclusion, we can state that integrated information allows the building of more reliable interaction networks. Identification of communities, cliques, modules and hubs by analysing the topological parameters and graph properties of the protein networks allows the discovery of central/critical nodes, which are candidates to regulate cellular flux and dynamics. PMID:22908212

  15. Introduction to machine learning.

    PubMed

    Baştanlar, Yalin; Ozuysal, Mustafa

    2014-01-01

    The machine learning field, which can be briefly defined as enabling computers make successful predictions using past experiences, has exhibited an impressive development recently with the help of the rapid increase in the storage capacity and processing power of computers. Together with many other disciplines, machine learning methods have been widely employed in bioinformatics. The difficulties and cost of biological analyses have led to the development of sophisticated machine learning approaches for this application area. In this chapter, we first review the fundamental concepts of machine learning such as feature assessment, unsupervised versus supervised learning and types of classification. Then, we point out the main issues of designing machine learning experiments and their performance evaluation. Finally, we introduce some supervised learning methods. PMID:24272434

  16. Synthesis of a pH-Sensitive Hetero[4]Rotaxane Molecular Machine that Combines [c2]Daisy and [2]Rotaxane Arrangements.

    PubMed

    Waelès, Philip; Riss-Yaw, Benjamin; Coutrot, Frédéric

    2016-05-10

    The synthesis of a novel pH-sensitive hetero[4]rotaxane molecular machine through a self-sorting strategy is reported. The original tetra-interlocked molecular architecture combines a [c2]daisy chain scaffold linked to two [2]rotaxane units. Actuation of the system through pH variation is possible thanks to the specific interactions of the dibenzo-24-crown-8 (DB24C8) macrocycles for ammonium, anilinium, and triazolium molecular stations. Selective deprotonation of the anilinium moieties triggers shuttling of the unsubstituted DB24C8 along the [2]rotaxane units. PMID:27062072

  17. Machine-Based Morphologic Analysis of Glioblastoma Using Whole-Slide Pathology Images Uncovers Clinically Relevant Molecular Correlates

    PubMed Central

    Kong, Jun; Cooper, Lee A. D.; Wang, Fusheng; Gao, Jingjing; Teodoro, George; Scarpace, Lisa; Mikkelsen, Tom; Schniederjan, Matthew J.; Moreno, Carlos S.; Saltz, Joel H.; Brat, Daniel J.

    2013-01-01

    Pathologic review of tumor morphology in histologic sections is the traditional method for cancer classification and grading, yet human review has limitations that can result in low reproducibility and inter-observer agreement. Computerized image analysis can partially overcome these shortcomings due to its capacity to quantitatively and reproducibly measure histologic structures on a large-scale. In this paper, we present an end-to-end image analysis and data integration pipeline for large-scale morphologic analysis of pathology images and demonstrate the ability to correlate phenotypic groups with molecular data and clinical outcomes. We demonstrate our method in the context of glioblastoma (GBM), with specific focus on the degree of the oligodendroglioma component. Over 200 million nuclei in digitized pathology slides from 117 GBMs in the Cancer Genome Atlas were quantitatively analyzed, followed by multiplatform correlation of nuclear features with molecular and clinical data. For each nucleus, a Nuclear Score (NS) was calculated based on the degree of oligodendroglioma appearance, using a regression model trained from the optimal feature set. Using the frequencies of neoplastic nuclei in low and high NS intervals, we were able to cluster patients into three well-separated disease groups that contained low, medium, or high Oligodendroglioma Component (OC). We showed that machine-based classification of GBMs with high oligodendroglioma component uncovered a set of tumors with strong associations with PDGFRA amplification, proneural transcriptional class, and expression of the oligodendrocyte signature genes MBP, HOXD1, PLP1, MOBP and PDGFRA. Quantitative morphologic features within the GBMs that correlated most strongly with oligodendrocyte gene expression were high nuclear circularity and low eccentricity. These findings highlight the potential of high throughput morphologic analysis to complement and inform human-based pathologic review. PMID:24236209

  18. Strategic sophistication of individuals and teams. Experimental evidence

    PubMed Central

    Sutter, Matthias; Czermak, Simon; Feri, Francesco

    2013-01-01

    Many important decisions require strategic sophistication. We examine experimentally whether teams act more strategically than individuals. We let individuals and teams make choices in simple games, and also elicit first- and second-order beliefs. We find that teams play the Nash equilibrium strategy significantly more often, and their choices are more often a best response to stated first order beliefs. Distributional preferences make equilibrium play less likely. Using a mixture model, the estimated probability to play strategically is 62% for teams, but only 40% for individuals. A model of noisy introspection reveals that teams differ from individuals in higher order beliefs. PMID:24926100

  19. Energy-based scheme for reconstruction of piecewise constant signals observed in the movement of molecular machines.

    PubMed

    Rosskopf, Joachim; Paul-Yuan, Korbinian; Plenio, Martin B; Michaelis, Jens

    2016-08-01

    Analyzing the physical and chemical properties of single DNA-based molecular machines such as polymerases and helicases requires to track stepping motion on the length scale of base pairs. Although high-resolution instruments have been developed that are capable of reaching that limit, individual steps are oftentimes hidden by experimental noise which complicates data processing. Here we present an effective two-step algorithm which detects steps in a high-bandwidth signal by minimizing an energy-based model (energy-based step finder, EBS). First, an efficient convex denoising scheme is applied which allows compression to tuples of amplitudes and plateau lengths. Second, a combinatorial clustering algorithm formulated on a graph is used to assign steps to the tuple data while accounting for prior information. Performance of the algorithm was tested on Poissonian stepping data simulated based on published kinetics data of RNA polymerase II (pol II). Comparison to existing step-finding methods shows that EBS is superior in speed while providing competitive step-detection results, especially in challenging situations. Moreover, the capability to detect backtracked intervals in experimental data of pol II as well as to detect stepping behavior of the Phi29 DNA packaging motor is demonstrated. PMID:27627346

  20. Muscle as a molecular machine for protecting joints and bones by absorbing mechanical impacts.

    PubMed

    Sarvazyan, Armen; Rudenko, Oleg; Aglyamov, Salavat; Emelianov, Stanislav

    2014-07-01

    We hypothesize that dissipation of mechanical energy of external impact to absorb mechanical shock is a fundamental function of skeletal muscle in addition to its primary function to convert chemical energy into mechanical energy. In physical systems, the common mechanism for absorbing mechanical shock is achieved with the use of both elastic and viscous elements and we hypothesize that the viscosity of the skeletal muscle is a variable parameter which can be voluntarily controlled by changing the tension of the contracting muscle. We further hypothesize that an ability of muscle to absorb shock has been an important factor in biological evolution, allowing the life to move from the ocean to land, from hydrodynamic to aerodynamic environment with dramatically different loading conditions for musculoskeletal system. The ability of muscle to redistribute the energy of mechanical shock in time and space and unload skeletal joints is of key importance in physical activities. We developed a mathematical model explaining the absorption of mechanical shock energy due to the increased viscosity of contracting skeletal muscles. The developed model, based on the classical theory of sliding filaments, demonstrates that the increased muscle viscosity is a result of the time delay (or phase shift) between the mechanical impact and the attachment/detachment of myosin heads to binding sites on the actin filaments. The increase in the contracted muscle's viscosity is time dependent. Since the forward and backward rate constants for binding the myosin heads to the actin filaments are on the order of 100s(-1), the viscosity of the contracted muscle starts to significantly increase with an impact time greater than 0.01s. The impact time is one of the key parameters in generating destructive stress in the colliding objects. In order to successfully dampen a short high power impact, muscles must first slow it down to engage the molecular mechanism of muscle viscosity. Muscle carries

  1. Fullerene Machines

    NASA Technical Reports Server (NTRS)

    Globus, Al; Saini, Subhash (Technical Monitor)

    1998-01-01

    Fullerenes possess remarkable properties and many investigators have examined the mechanical, electronic and other characteristics of carbon SP2 systems in some detail. In addition, C-60 can be functionalized with many classes of molecular fragments and we may expect the caps of carbon nanotubes to have a similar chemistry. Finally, carbon nanotubes have been attached to t he end of scanning probe microscope (Spill) tips. Spills can be manipulated with sub-angstrom accuracy. Together, these investigations suggest that complex molecular machines made of fullerenes may someday be created and manipulated with very high accuracy. We have studied some such systems computationally (primarily functionalized carbon nanotube gears and computer components). If such machines can be combined appropriately, a class of materials may be created that can sense their environment, calculate a response, and act. The implications of such hypothetical materials are substantial.

  2. Machine-learning approach for one- and two-body corrections to density functional theory: Applications to molecular and condensed water

    NASA Astrophysics Data System (ADS)

    Bartók, Albert P.; Gillan, Michael J.; Manby, Frederick R.; Csányi, Gábor

    2013-08-01

    We show how machine learning techniques based on Bayesian inference can be used to enhance the computer simulation of molecular materials, focusing here on water. We train our machine-learning algorithm using accurate, correlated quantum chemistry, and predict energies and forces in molecular aggregates ranging from clusters to solid and liquid phases. The widely used electronic-structure methods based on density functional theory (DFT) by themselves give poor accuracy for molecular materials like water, and we show how our techniques can be used to generate systematically improvable one- and two-body corrections to DFT with modest extra resources. The resulting corrected DFT scheme is considerably more accurate than uncorrected DFT for the relative energies of small water clusters and different ice structures and significantly improves the description of the structure and dynamics of liquid water. However, our results for ice structures and the liquid indicate that beyond-two-body DFT errors cannot be ignored, and we suggest how our machine-learning methods can be further developed to correct these errors.

  3. Data mining PubChem using a support vector machine with the Signature molecular descriptor: classification of factor XIa inhibitors.

    PubMed

    Weis, Derick C; Visco, Donald P; Faulon, Jean-Loup

    2008-11-01

    The amount of high-throughput screening (HTS) data readily available has significantly increased because of the PubChem project (http://pubchem.ncbi.nlm.nih.gov/). There is considerable opportunity for data mining of small molecules for a variety of biological systems using cheminformatic tools and the resources available through PubChem. In this work, we trained a support vector machine (SVM) classifier using the Signature molecular descriptor on factor XIa inhibitor HTS data. The optimal number of Signatures was selected by implementing a feature selection algorithm of highly correlated clusters. Our method included an improvement that allowed clusters to work together for accuracy improvement, where previous methods have scored clusters on an individual basis. The resulting model had a 10-fold cross-validation accuracy of 89%, and additional validation was provided by two independent test sets. We applied the SVM to rapidly predict activity for approximately 12 million compounds also deposited in PubChem. Confidence in these predictions was assessed by considering the number of Signatures within the training set range for a given compound, defined as the overlap metric. To further evaluate compounds identified as active by the SVM, docking studies were performed using AutoDock. A focused database of compounds predicted to be active was obtained with several of the compounds appreciably dissimilar to those used in training the SVM. This focused database is suitable for further study. The data mining technique presented here is not specific to factor XIa inhibitors, and could be applied to other bioassays in PubChem where one is looking to expand the search for small molecules as chemical probes. PMID:18829357

  4. Sophisticated Communication in the Brazilian Torrent Frog Hylodes japi.

    PubMed

    de Sá, Fábio P; Zina, Juliana; Haddad, Célio F B

    2016-01-01

    Intraspecific communication in frogs plays an important role in the recognition of conspecifics in general and of potential rivals or mates in particular and therefore with relevant consequences for pre-zygotic reproductive isolation. We investigate intraspecific communication in Hylodes japi, an endemic Brazilian torrent frog with territorial males and an elaborate courtship behavior. We describe its repertoire of acoustic signals as well as one of the most complex repertoires of visual displays known in anurans, including five new visual displays. Previously unknown in frogs, we also describe a bimodal inter-sexual communication system where the female stimulates the male to emit a courtship call. As another novelty for frogs, we show that in addition to choosing which limb to signal with, males choose which of their two vocal sacs will be used for visual signaling. We explain how and why this is accomplished. Control of inflation also provides additional evidence that vocal sac movement and color must be important for visual communication, even while producing sound. Through the current knowledge on visual signaling in Neotropical torrent frogs (i.e. hylodids), we discuss and highlight the behavioral diversity in the family Hylodidae. Our findings indicate that communication in species of Hylodes is undoubtedly more sophisticated than we expected and that visual communication in anurans is more widespread than previously thought. This is especially true in tropical regions, most likely due to the higher number of species and phylogenetic groups and/or to ecological factors, such as higher microhabitat diversity. PMID:26760304

  5. Competition drives sophisticated hunting skills of archerfish in the wild.

    PubMed

    Rischawy, Ingo; Blum, Michael; Schuster, Stefan

    2015-07-20

    Several animals are renowned for their cognitive skills, such as tool use, metacognition or social learning. However, it remains puzzling why some species excel whereas others - sometimes even closely related ones - do not. Archerfish show a remarkable assembly of skills in the context of their unique hunting behavior in which they down aerial prey with shots of water. Hoping to find ecological factors behind these skills, we have over the past years regularly traveled to archerfish mangrove habitats in Thailand (Figure 1A). One of our most consistent findings was the presence of other surface-feeding fish, particularly the similar-sized halfbeak Zenarchopterus buffonis, wherever we spotted groups of archerfish (Figure 1A; Supplemental movie S1). We describe here that Zenarchopterus is superbly equipped with water-wave detectors, rapidly detects the impact of prey even in the dark, is active at all times, is usually more numerous than archerfish and supplements its capabilities with visual skills. Without sophisticated additions to their hunting technique archerfish would thus lose most of their downed prey to halfbeaks. We suggest that the evolution of several skills of archerfish may have thus been influenced not only by intraspecific competition [5] but also by competition with other surface-feeding fish species. PMID:26196481

  6. Sophisticated Communication in the Brazilian Torrent Frog Hylodes japi

    PubMed Central

    de Sá, Fábio P.; Zina, Juliana; Haddad, Célio F. B.

    2016-01-01

    Intraspecific communication in frogs plays an important role in the recognition of conspecifics in general and of potential rivals or mates in particular and therefore with relevant consequences for pre-zygotic reproductive isolation. We investigate intraspecific communication in Hylodes japi, an endemic Brazilian torrent frog with territorial males and an elaborate courtship behavior. We describe its repertoire of acoustic signals as well as one of the most complex repertoires of visual displays known in anurans, including five new visual displays. Previously unknown in frogs, we also describe a bimodal inter-sexual communication system where the female stimulates the male to emit a courtship call. As another novelty for frogs, we show that in addition to choosing which limb to signal with, males choose which of their two vocal sacs will be used for visual signaling. We explain how and why this is accomplished. Control of inflation also provides additional evidence that vocal sac movement and color must be important for visual communication, even while producing sound. Through the current knowledge on visual signaling in Neotropical torrent frogs (i.e. hylodids), we discuss and highlight the behavioral diversity in the family Hylodidae. Our findings indicate that communication in species of Hylodes is undoubtedly more sophisticated than we expected and that visual communication in anurans is more widespread than previously thought. This is especially true in tropical regions, most likely due to the higher number of species and phylogenetic groups and/or to ecological factors, such as higher microhabitat diversity. PMID:26760304

  7. Fullerene Machines

    NASA Technical Reports Server (NTRS)

    Globus, Al; Saini, Subhash

    1998-01-01

    Recent computational efforts at NASA Ames Research Center and computation and experiment elsewhere suggest that a nanotechnology of machine phase functionalized fullerenes may be synthetically accessible and of great interest. We have computationally demonstrated that molecular gears fashioned from (14,0) single-walled carbon nanotubes and benzyne teeth should operate well at 50-100 gigahertz. Preliminary results suggest that these gears can be cooled by a helium atmosphere and a laser motor can power fullerene gears if a positive and negative charge have been added to form a dipole. In addition, we have unproven concepts based on experimental and computational evidence for support structures, computer control, a system architecture, a variety of components, and manufacture. Combining fullerene machines with the remarkable mechanical properties of carbon nanotubes, there is some reason to believe that a focused effort to develop fullerene nanotechnology could yield materials with tremendous properties.

  8. Library of sophisticated functions for analysis of nuclear spectra

    NASA Astrophysics Data System (ADS)

    Morháč, Miroslav; Matoušek, Vladislav

    2009-10-01

    In the paper we present compact library for analysis of nuclear spectra. The library consists of sophisticated functions for background elimination, smoothing, peak searching, deconvolution, and peak fitting. The functions can process one- and two-dimensional spectra. The software described in the paper comprises a number of conventional as well as newly developed methods needed to analyze experimental data. Program summaryProgram title: SpecAnalysLib 1.1 Catalogue identifier: AEDZ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEDZ_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 42 154 No. of bytes in distributed program, including test data, etc.: 2 379 437 Distribution format: tar.gz Programming language: C++ Computer: Pentium 3 PC 2.4 GHz or higher, Borland C++ Builder v. 6. A precompiled Windows version is included in the distribution package Operating system: Windows 32 bit versions RAM: 10 MB Word size: 32 bits Classification: 17.6 Nature of problem: The demand for advanced highly effective experimental data analysis functions is enormous. The library package represents one approach to give the physicists the possibility to use the advanced routines simply by calling them from their own programs. SpecAnalysLib is a collection of functions for analysis of one- and two-parameter γ-ray spectra, but they can be used for other types of data as well. The library consists of sophisticated functions for background elimination, smoothing, peak searching, deconvolution, and peak fitting. Solution method: The algorithms of background estimation are based on Sensitive Non-linear Iterative Peak (SNIP) clipping algorithm. The smoothing algorithms are based on the convolution of the original data with several types of filters and algorithms based on discrete

  9. Elements in nucleotide sensing and hydrolysis of the AAA+ disaggregation machine ClpB: a structure-based mechanistic dissection of a molecular motor

    SciTech Connect

    Zeymer, Cathleen Barends, Thomas R. M.; Werbeck, Nicolas D.; Schlichting, Ilme; Reinstein, Jochen

    2014-02-01

    High-resolution crystal structures together with mutational analysis and transient kinetics experiments were utilized to understand nucleotide sensing and the regulation of the ATPase cycle in an AAA+ molecular motor. ATPases of the AAA+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from ATP hydrolysis into mechanical force. This study focuses on the molecular chaperone ClpB, the bacterial homologue of Hsp104, which reactivates aggregated proteins under cellular stress conditions. Based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2), one of the motor subunits of this AAA+ disaggregation machine, is dissected mechanistically. The results provide insights into nucleotide sensing, explaining how the conserved sensor 2 motif contributes to the discrimination between ADP and ATP binding. Furthermore, the role of a conserved active-site arginine (Arg621), which controls binding of the essential Mg{sup 2+} ion, is described. Finally, a hypothesis is presented as to how the ATPase activity is regulated by a conformational switch that involves the essential Walker A lysine. In the proposed model, an unusual side-chain conformation of this highly conserved residue stabilizes a catalytically inactive state, thereby avoiding unnecessary ATP hydrolysis.

  10. Analysis of functional motions in Brownian molecular machines with an efficient block normal mode approach: myosin-II and Ca2+ -ATPase.

    PubMed

    Li, Guohui; Cui, Qiang

    2004-02-01

    The structural flexibilities of two molecular machines, myosin and Ca(2+)-ATPase, have been analyzed with normal mode analysis and discussed in the context of their energy conversion functions. The normal mode analysis with physical intermolecular interactions was made possible by an improved implementation of the block normal mode (BNM) approach. The BNM results clearly illustrated that the large-scale conformational transitions implicated in the functional cycles of the two motor systems can be largely captured with a small number of low-frequency normal modes. Therefore, the results support the idea that structural flexibility is an essential part of the construction principle of molecular motors through evolution. Such a feature is expected to be more prevalent in motor proteins than in simpler systems (e.g., signal transduction proteins) because in the former, large-scale conformational transitions often have to occur before the chemical events (e.g., ATP hydrolysis in myosin and ATP binding/phosphorylation in Ca(2+)-ATPase). This highlights the importance of Brownian motions associated with the protein domains that are involved in the functional transitions; in this sense, Brownian molecular machines is an appropriate description of molecular motors, although the normal mode results do not address the origin of the ratchet effect. The results also suggest that it might be more appropriate to describe functional transitions in some molecular motors as intrinsic elastic motions modulating local structural changes in the active site, which in turn gets stabilized by the subsequent chemical events, in contrast with the conventional idea of local changes somehow getting amplified into larger-scale motions. In the case of myosin, for example, we favor the idea that Brownian motions associated with the flexible converter propagates to the Switch I/II region, where the salt-bridge formation gets stabilized by ATP hydrolysis, in contrast with the textbook notion that

  11. Sophisticated Search Capabilities in the ADS Abstract Service

    NASA Astrophysics Data System (ADS)

    Eichhorn, G.; Accomazzi, A.; Grant, C. S.; Henneken, E.; Kurtz, M. J.; Murray, S. S.

    2003-12-01

    The ADS provides access to over 940,000 references from astronomy and planetary sciences publications and 1.5 million records from physics publications. It is funded by NASA and provides free access to these references, as well as to 2.4 million scanned pages from the astronomical literature. These include most of the major astronomy and several planetary sciences journals, as well as many historical observatory publications. The references now include the abstracts from all volumes of the Journal of Geophysical Research (JGR) since the beginning of 2002. We get these abstracts on a regular basis. The Kluwer journal Solar Physics has been scanned back to volume 1 and is available through the ADS. We have extracted the reference lists from this and many other journals and included them in the reference and citation database of the ADS. We have recently scanning Earth, Moon and Planets, another Kluwer journal, and will scan other Kluwer journals in the future as well. We plan on extracting references from these journals as well in the near future. The ADS has many sophisticated query features. These allow the user to formulate complex queries. Using results lists to get further information about the selected articles provide the means to quickly find important and relevant articles from the database. Three advanced feedback queries are available from the bottom of the ADS results list (in addition to regular feedback queries already available from the abstract page and from the bottom of the results list): 1. Get reference list for selected articles: This query returns all known references for the selected articles (or for all articles in the first list). The resulting list will be ranked according to how often each article is referred to and will show the most referenced articles in the field of study that created the first list. It presumably shows the most important articles in that field. 2. Get citation list for selected articles: This returns all known articles

  12. Business Machines

    ERIC Educational Resources Information Center

    Pactor, Paul

    1970-01-01

    The U.S. Department of Labor has projected a 106 percent increase in the demand for office machine operators over the next 10 years. Machines with a high frequency of use include printing calculators, 10-key adding machines, and key punch machines. The 12th grade is the logical time for teaching business machines. (CH)

  13. Characteristics and Levels of Sophistication: An Analysis of Chemistry Students' Ability to Think with Mental Models

    NASA Astrophysics Data System (ADS)

    Wang, Chia-Yu; Barrow, Lloyd H.

    2011-08-01

    This study employed a case-study approach to reveal how an ability to think with mental models contributes to differences in students' understanding of molecular geometry and polarity. We were interested in characterizing features and levels of sophistication regarding first-year university chemistry learners' mental modeling behaviors while the learners were solving problems associated with spatial information. To serve this purpose, we conducted case studies on nine students who were sampled from high-scoring, moderate-scoring, and low-scoring students. Our findings point to five characteristics of mental modeling ability that distinguish students in the high-, moderate-, and low-ability groups from one another. Although the levels of mental modeling abilities have been described in categories (high, moderate, and low), they can be thought of as a continuum with the low-ability group reflecting students who have very limited ability to generate and use mental models whereas students in the high-ability group not only construct and use mental models as a thinking tool, but also analyze the problems to be solved, evaluate their mental models, and oversee entire mental modeling processes. Cross-case comparisons for students with different levels of mental modeling ability indicate that experiences of generating and manipulating a mental model based on imposed propositions are crucial for a learner's efforts to incorporate content knowledge with visual-spatial thinking skills. This paper summarizes potential factors that undermine learners' comprehension of molecular geometry and polarity and that influence mastery of this mental modeling ability.

  14. Machine Shop Grinding Machines.

    ERIC Educational Resources Information Center

    Dunn, James

    This curriculum manual is one in a series of machine shop curriculum manuals intended for use in full-time secondary and postsecondary classes, as well as part-time adult classes. The curriculum can also be adapted to open-entry, open-exit programs. Its purpose is to equip students with basic knowledge and skills that will enable them to enter the…

  15. Isocratean Discourse Theory and Neo-Sophistic Pedagogy: Implications for the Composition Classroom.

    ERIC Educational Resources Information Center

    Blair, Kristine L.

    With the recent interest in the fifth century B.C. theories of Protagoras and Gorgias come assumptions about the philosophical affinity of the Greek educator Isocrates to this pair of older sophists. Isocratean education in discourse, with its emphasis on collaborative political discourse, falls within recent definitions of a sophist curriculum.…

  16. From Poetry to Prose: Sophistic Rhetoric and the Epistemic Music of Language.

    ERIC Educational Resources Information Center

    Katz, Steven B.

    Much revisionist scholarship has focused on sophistic epistemology and its relationship to the current revival of epistemic rhetoric in the academy. However, few scholars have recognized the sensuous substance of words as sounds, and the role it played in sophistic philosophy and rhetoric. Before the invention of the Greek alphabet, poetry was…

  17. Database machines

    NASA Technical Reports Server (NTRS)

    Stiefel, M. L.

    1983-01-01

    The functions and performance characteristics of data base machines (DBM), including machines currently being studied in research laboratories and those currently offered on a commerical basis are discussed. The cost/benefit considerations that must be recognized in selecting a DBM are discussed, as well as the future outlook for such machines.

  18. DNA-based machines.

    PubMed

    Wang, Fuan; Willner, Bilha; Willner, Itamar

    2014-01-01

    The base sequence in nucleic acids encodes substantial structural and functional information into the biopolymer. This encoded information provides the basis for the tailoring and assembly of DNA machines. A DNA machine is defined as a molecular device that exhibits the following fundamental features. (1) It performs a fuel-driven mechanical process that mimics macroscopic machines. (2) The mechanical process requires an energy input, "fuel." (3) The mechanical operation is accompanied by an energy consumption process that leads to "waste products." (4) The cyclic operation of the DNA devices, involves the use of "fuel" and "anti-fuel" ingredients. A variety of DNA-based machines are described, including the construction of "tweezers," "walkers," "robots," "cranes," "transporters," "springs," "gears," and interlocked cyclic DNA structures acting as reconfigurable catenanes, rotaxanes, and rotors. Different "fuels", such as nucleic acid strands, pH (H⁺/OH⁻), metal ions, and light, are used to trigger the mechanical functions of the DNA devices. The operation of the devices in solution and on surfaces is described, and a variety of optical, electrical, and photoelectrochemical methods to follow the operations of the DNA machines are presented. We further address the possible applications of DNA machines and the future perspectives of molecular DNA devices. These include the application of DNA machines as functional structures for the construction of logic gates and computing, for the programmed organization of metallic nanoparticle structures and the control of plasmonic properties, and for controlling chemical transformations by DNA machines. We further discuss the future applications of DNA machines for intracellular sensing, controlling intracellular metabolic pathways, and the use of the functional nanostructures for drug delivery and medical applications. PMID:24647836

  19. Prediction of novel and selective TNF-alpha converting enzyme (TACE) inhibitors and characterization of correlative molecular descriptors by machine learning approaches.

    PubMed

    Cong, Yong; Yang, Xue-Gang; Lv, Wei; Xue, Ying

    2009-10-01

    The inhibition of TNF-alpha converting enzyme (TACE) has been explored as a feasible therapy for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Recently, large numbers of novel and selective TACE inhibitors have been reported. It is desirable to develop machine learning (ML) models for identifying the inhibitors of TACE in the early drug design phase and test the prediction capabilities of these ML models. This work evaluated four ML methods, support vector machine (SVM), k-nearest neighbor (k-NN), back-propagation neural network (BPNN) and C4.5 decision tree (C4.5 DT), which were trained and tested by using a diverse set of 443 TACE inhibitors and 759 non-inhibitors. A well-established feature selection method, the recursive feature elimination (RFE) method, was used to select the most appropriate descriptors for classification from a large pool of descriptors, and two evaluation methods, 5-fold cross-validation and independent evaluation, were used to assess the performances of these developed models. In this study, all these ML models have already achieved promising prediction accuracies. By using the RFE method, the prediction accuracies are further improved. In k-NN, the model gives the best prediction for TACE inhibitors (98.32%), and the SVM bears the best prediction for non-inhibitors (99.51%). Both the k-NN and SVM model give the best overall prediction accuracy (98.45%). To the best of our knowledge, the SVM model developed in this work is the first one for the classification prediction of TACE inhibitors with a broad applicability domain. Our study suggests that ML methods, particularly SVM, are potentially useful for facilitating the discovery of TACE inhibitors and for exhibiting the molecular descriptors associated with TACE inhibitors. PMID:19729328

  20. In Silico Calculation of Infinite Dilution Activity Coefficients of Molecular Solutes in Ionic Liquids: Critical Review of Current Methods and New Models Based on Three Machine Learning Algorithms.

    PubMed

    Paduszyński, Kamil

    2016-08-22

    The aim of the paper is to address all the disadvantages of currently available models for calculating infinite dilution activity coefficients (γ(∞)) of molecular solutes in ionic liquids (ILs)-a relevant property from the point of view of many applications of ILs, particularly in separations. Three new models are proposed, each of them based on distinct machine learning algorithm: stepwise multiple linear regression (SWMLR), feed-forward artificial neural network (FFANN), and least-squares support vector machine (LSSVM). The models were established based on the most comprehensive γ(∞) data bank reported so far (>34 000 data points for 188 ILs and 128 solutes). Following the paper published previously [J. Chem. Inf. Model 2014, 54, 1311-1324], the ILs were treated in terms of group contributions, whereas the Abraham solvation parameters were used to quantify an impact of solute structure. Temperature is also included in the input data of the models so that they can be utilized to obtain temperature-dependent data and thus related thermodynamic functions. Both internal and external validation techniques were applied to assess the statistical significance and explanatory power of the final correlations. A comparative study of the overall performance of the investigated SWMLR/FFANN/LSSVM approaches is presented in terms of root-mean-square error and average absolute relative deviation between calculated and experimental γ(∞), evaluated for different families of ILs and solutes, as well as between calculated and experimental infinite dilution selectivity for separation problems benzene from n-hexane and thiophene from n-heptane. LSSVM is shown to be a method with the lowest values of both training and generalization errors. It is finally demonstrated that the established models exhibit an improved accuracy compared to the state-of-the-art model, namely, temperature-dependent group contribution linear solvation energy relationship, published in 2011 [J. Chem

  1. 15 CFR 768.10 - Removal of controls on less sophisticated items.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION... sophisticated items. Where the Secretary has removed national security controls on an item for foreign... security reasons and whose functions, technological approach, performance thresholds, and other...

  2. 15 CFR 768.10 - Removal of controls on less sophisticated items.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION... sophisticated items. Where the Secretary has removed national security controls on an item for foreign... security reasons and whose functions, technological approach, performance thresholds, and other...

  3. 15 CFR 768.10 - Removal of controls on less sophisticated items.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION... sophisticated items. Where the Secretary has removed national security controls on an item for foreign... security reasons and whose functions, technological approach, performance thresholds, and other...

  4. 15 CFR 768.10 - Removal of controls on less sophisticated items.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION... sophisticated items. Where the Secretary has removed national security controls on an item for foreign... security reasons and whose functions, technological approach, performance thresholds, and other...

  5. 15 CFR 768.10 - Removal of controls on less sophisticated items.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION... sophisticated items. Where the Secretary has removed national security controls on an item for foreign... security reasons and whose functions, technological approach, performance thresholds, and other...

  6. Prediction of overall in vitro microsomal stability of drug candidates based on molecular modeling and support vector machines. Case study of novel arylpiperazines derivatives.

    PubMed

    Ulenberg, Szymon; Belka, Mariusz; Król, Marek; Herold, Franciszek; Hewelt-Belka, Weronika; Kot-Wasik, Agata; Bączek, Tomasz

    2015-01-01

    Other than efficacy of interaction with the molecular target, metabolic stability is the primary factor responsible for the failure or success of a compound in the drug development pipeline. The ideal drug candidate should be stable enough to reach its therapeutic site of action. Despite many recent excellent achievements in the field of computational methods supporting drug metabolism studies, a well-recognized procedure to model and predict metabolic stability quantitatively is still lacking. This study proposes a workflow for developing quantitative metabolic stability-structure relationships, taking a set of 30 arylpiperazine derivatives as an example. The metabolic stability of the compounds was assessed in in vitro incubations in the presence of human liver microsomes and NADPH and subsequently quantified by liquid chromatography-mass spectrometry (LC-MS). Density functional theory (DFT) calculations were used to obtain 30 models of the molecules, and Dragon software served as a source of structure-based molecular descriptors. For modeling structure-metabolic stability relationships, Support Vector Machines (SVM), a non-linear machine learning technique, were found to be more effective than a regression technique, based on the validation parameters obtained. Moreover, for the first time, general sites of metabolism for arylpiperazines bearing the 4-aryl-2H-pyrido[1,2-c]pyrimidine-1,3-dione system were defined by analysis of Q-TOF-MS/MS spectra. The results indicated that the application of one of the most advanced chemometric techniques combined with a simple and quick in vitro procedure and LC-MS analysis provides a novel and valuable tool for predicting metabolic half-life values. Given the reduced time and simplicity of analysis, together with the accuracy of the predictions obtained, this is a valid approach for predicting metabolic stability using structural data. The approach presented provides a novel, comprehensive and reliable tool for investigating

  7. A System for Conducting Sophisticated Mechanical Tests in Situ with High Energy Synchrotron X-Rays Final Technical Report

    SciTech Connect

    Jeremy Weiss

    2012-08-02

    This is the final technical report for the SBIR Phase I project titled 'A System for Conducting Sophisticated Mechanical Tests in Situ with High Energy Synchrotron X-Rays.' Experiments using diffraction of synchrotron radiation that help scientists understand engineering material failure modes, such as fracture and fatigue, require specialized machinery. This machinery must be able to induce these failure modes in a material specimen while adhering to strict size, weight, and geometric limitations prescribed by diffraction measurement techniques. During this Phase I project, Mechanical Solutions, Inc. (MSI) developed one such machine capable of applying uniaxial mechanical loading to a material specimen in both tension and compression, with zero backlash while transitioning between the two. Engineers currently compensate for a lack of understanding of fracture and fatigue by employing factors of safety in crucial system components. Thus, mechanical and structural parts are several times bigger, thicker, and heavier than they need to be. The scientific discoveries that result from diffraction experiments which utilize sophisticated mechanical loading devices will allow for broad material, weight, fuel, and cost savings in engineering design across all industries, while reducing the number of catastrophic failures in transportation, power generation, infrastructure, and all other engineering systems. With an existing load frame as the starting point, the research focused on two main areas: (1) the design of a specimen alignment and gripping system that enables pure uniaxial tension and compression loading (and no bending, shear, or torsion), and (2) development of a feedback control system that is adaptive and thus can maintain a load set point despite changing specimen material properties (e.g. a decreasing stiffness during yield).

  8. Moral foundations and political attitudes: The moderating role of political sophistication.

    PubMed

    Milesi, Patrizia

    2016-08-01

    Political attitudes can be associated with moral concerns. This research investigated whether people's level of political sophistication moderates this association. Based on the Moral Foundations Theory, this article examined whether political sophistication moderates the extent to which reliance on moral foundations, as categories of moral concerns, predicts judgements about policy positions. With this aim, two studies examined four policy positions shown by previous research to be best predicted by the endorsement of Sanctity, that is, the category of moral concerns focused on the preservation of physical and spiritual purity. The results showed that reliance on Sanctity predicted political sophisticates' judgements, as opposed to those of unsophisticates, on policy positions dealing with equal rights for same-sex and unmarried couples and with euthanasia. Political sophistication also interacted with Fairness endorsement, which includes moral concerns for equal treatment of everybody and reciprocity, in predicting judgements about equal rights for unmarried couples, and interacted with reliance on Authority, which includes moral concerns for obedience and respect for traditional authorities, in predicting opposition to stem cell research. Those findings suggest that, at least for these particular issues, endorsement of moral foundations can be associated with political attitudes more strongly among sophisticates than unsophisticates. PMID:25727878

  9. The musicality of non-musicians: an index for assessing musical sophistication in the general population.

    PubMed

    Müllensiefen, Daniel; Gingras, Bruno; Musil, Jason; Stewart, Lauren

    2014-01-01

    Musical skills and expertise vary greatly in Western societies. Individuals can differ in their repertoire of musical behaviours as well as in the level of skill they display for any single musical behaviour. The types of musical behaviours we refer to here are broad, ranging from performance on an instrument and listening expertise, to the ability to employ music in functional settings or to communicate about music. In this paper, we first describe the concept of 'musical sophistication' which can be used to describe the multi-faceted nature of musical expertise. Next, we develop a novel measurement instrument, the Goldsmiths Musical Sophistication Index (Gold-MSI) to assess self-reported musical skills and behaviours on multiple dimensions in the general population using a large Internet sample (n = 147,636). Thirdly, we report results from several lab studies, demonstrating that the Gold-MSI possesses good psychometric properties, and that self-reported musical sophistication is associated with performance on two listening tasks. Finally, we identify occupation, occupational status, age, gender, and wealth as the main socio-demographic factors associated with musical sophistication. Results are discussed in terms of theoretical accounts of implicit and statistical music learning and with regard to social conditions of sophisticated musical engagement. PMID:24586929

  10. Nonplanar machines

    SciTech Connect

    Ritson, D. )

    1989-05-01

    This talk examines methods available to minimize, but never entirely eliminate, degradation of machine performance caused by terrain following. Breaking of planar machine symmetry for engineering convenience and/or monetary savings must be balanced against small performance degradation, and can only be decided on a case-by-case basis. 5 refs.

  11. Electric machine

    DOEpatents

    El-Refaie, Ayman Mohamed Fawzi; Reddy, Patel Bhageerath

    2012-07-17

    An interior permanent magnet electric machine is disclosed. The interior permanent magnet electric machine comprises a rotor comprising a plurality of radially placed magnets each having a proximal end and a distal end, wherein each magnet comprises a plurality of magnetic segments and at least one magnetic segment towards the distal end comprises a high resistivity magnetic material.

  12. Permutation Machines.

    PubMed

    Bhatia, Swapnil; LaBoda, Craig; Yanez, Vanessa; Haddock-Angelli, Traci; Densmore, Douglas

    2016-08-19

    We define a new inversion-based machine called a permuton of n genetic elements, which allows the n elements to be rearranged in any of the n·(n - 1)·(n - 2)···2 = n! distinct orderings. We present two design algorithms for architecting such a machine. We define a notion of a feasible design and use the framework to discuss the feasibility of the permuton architectures. We have implemented our design algorithms in a freely usable web-accessible software for exploration of these machines. Permutation machines could be used as memory elements or state machines and explicitly illustrate a rational approach to designing biological systems. PMID:27383067

  13. Differential ethnic associations between maternal flexibility and play sophistication in toddlers born very low birth weight

    PubMed Central

    Erickson, Sarah J.; Montague, Erica Q.; Maclean, Peggy C.; Bancroft, Mary E.; Lowe, Jean R.

    2013-01-01

    Children born very low birth weight (<1500 grams, VLBW) are at increased risk for developmental delays. Play is an important developmental outcome to the extent that child’s play and social communication are related to later development of self-regulation and effective functional skills, and play serves as an important avenue of early intervention. The current study investigated associations between maternal flexibility and toddler play sophistication in Caucasian, Spanish speaking Hispanic, English speaking Hispanic, and Native American toddlers (18-22 months adjusted age) in a cross-sectional cohort of 73 toddlers born VLBW and their mothers. We found that the association between maternal flexibility and toddler play sophistication differed by ethnicity (F(3,65) = 3.34, p = .02). In particular, Spanish speaking Hispanic dyads evidenced a significant positive association between maternal flexibility and play sophistication of medium effect size. Results for Native Americans were parallel to those of Spanish speaking Hispanic dyads: the relationship between flexibility and play sophistication was positive and of small-medium effect size. Findings indicate that for Caucasians and English speaking Hispanics, flexibility evidenced a non-significant (negative and small effect size) association with toddler play sophistication. Significant follow-up contrasts revealed that the associations for Caucasian and English speaking Hispanic dyads were significantly different from those of the other two ethnic groups. Results remained unchanged after adjusting for the amount of maternal language, an index of maternal engagement and stimulation; and after adjusting for birth weight, gestational age, gender, test age, cognitive ability, as well maternal age, education, and income. Our results provide preliminary evidence that ethnicity and acculturation may mediate the association between maternal interactive behavior such as flexibility and toddler developmental outcomes, as

  14. The Sophistication of Reading Interests as Related to Selected Personality Factors and Certain Other Characteristics of High School Students.

    ERIC Educational Resources Information Center

    Zais, Robert Stanley

    This study attempted to estimate by objective means the level of sophistication of high school students' interest in fiction and to determine the degree to which sophistication was related to selected personality factors and to sex, age, intelligence, and reading achievement. A scale was developed to measure sophistication of reading interests; a…

  15. Rational thinking and cognitive sophistication: development, cognitive abilities, and thinking dispositions.

    PubMed

    Toplak, Maggie E; West, Richard F; Stanovich, Keith E

    2014-04-01

    We studied developmental trends in 5 important reasoning tasks that are critical components of the operational definition of rational thinking. The tasks measured denominator neglect, belief bias, base rate sensitivity, resistance to framing, and the tendency toward otherside thinking. In addition to age, we examined 2 other individual difference domains that index cognitive sophistication: cognitive ability (intelligence and executive functioning) and thinking dispositions (actively open-minded thinking, superstitious thinking, and need for cognition). All 5 reasoning domains were consistently related to cognitive sophistication regardless of how it was indexed (age, cognitive ability, thinking dispositions). The implications of these findings for taxonomies of developmental trends in rational thinking tasks are discussed. PMID:24188038

  16. Assessing Epistemic Sophistication by Considering Domain-Specific Absolute and Multiplicistic Beliefs Separately

    ERIC Educational Resources Information Center

    Peter, Johannes; Rosman, Tom; Mayer, Anne-Kathrin; Leichner, Nikolas; Krampen, Günter

    2016-01-01

    Background: Particularly in higher education, not only a view of science as a means of finding absolute truths (absolutism), but also a view of science as generally tentative (multiplicism) can be unsophisticated and obstructive for learning. Most quantitative epistemic belief inventories neglect this and understand epistemic sophistication as…

  17. Interactive E-Assessment--Practical Approaches to Constructing More Sophisticated Online Tasks

    ERIC Educational Resources Information Center

    Crisp, Geoffrey

    2010-01-01

    This paper will explore some of the practical options that are available to teachers as we move towards Assessment 2.0. Assessment 2.0 describes an environment in which the teacher sets tasks that allow students to use more dynamic, immersive and interactive environments for exploring and creating responses to sophisticated assessment tasks.…

  18. Predicting Second Language Writing Proficiency: The Roles of Cohesion and Linguistic Sophistication

    ERIC Educational Resources Information Center

    Crossley, Scott A.; McNamara, Danielle S.

    2012-01-01

    This study addresses research gaps in predicting second language (L2) writing proficiency using linguistic features. Key to this analysis is the inclusion of linguistic measures at the surface, textbase and situation model level that assess text cohesion and linguistic sophistication. The results of this study demonstrate that five variables…

  19. The Musicality of Non-Musicians: An Index for Assessing Musical Sophistication in the General Population

    PubMed Central

    Müllensiefen, Daniel; Gingras, Bruno; Musil, Jason; Stewart, Lauren

    2014-01-01

    Musical skills and expertise vary greatly in Western societies. Individuals can differ in their repertoire of musical behaviours as well as in the level of skill they display for any single musical behaviour. The types of musical behaviours we refer to here are broad, ranging from performance on an instrument and listening expertise, to the ability to employ music in functional settings or to communicate about music. In this paper, we first describe the concept of ‘musical sophistication’ which can be used to describe the multi-faceted nature of musical expertise. Next, we develop a novel measurement instrument, the Goldsmiths Musical Sophistication Index (Gold-MSI) to assess self-reported musical skills and behaviours on multiple dimensions in the general population using a large Internet sample (n = 147,636). Thirdly, we report results from several lab studies, demonstrating that the Gold-MSI possesses good psychometric properties, and that self-reported musical sophistication is associated with performance on two listening tasks. Finally, we identify occupation, occupational status, age, gender, and wealth as the main socio-demographic factors associated with musical sophistication. Results are discussed in terms of theoretical accounts of implicit and statistical music learning and with regard to social conditions of sophisticated musical engagement. PMID:24586929

  20. Mining machine

    SciTech Connect

    Parrott, G.A.

    1985-05-07

    A haulage system for a mining machine comprises a mining machine mounted on and/or guided by a conveyor and reciprocable with respect thereto, the conveyor being provided with a rack having plural rows of teeth of identical pitch, with the teeth of one row staggered with respect to an adjacent row(s), and the machine being provided with at least one power driven haulage sprocket comprising plural sets of peripherally arranged teeth of identical pitch, one set being angularly staggered with respect to an adjacent set(s), whereby one set is engageable with each row of teeth of the rack. The invention also includes a mining machine provided with such a power driven haulage sprocket, and a rack as above described and provided with end fittings for securing in articulated manner to an adjacent rack.

  1. Monel Machining

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Castle Industries, Inc. is a small machine shop manufacturing replacement plumbing repair parts, such as faucet, tub and ballcock seats. Therese Castley, president of Castle decided to introduce Monel because it offered a chance to improve competitiveness and expand the product line. Before expanding, Castley sought NERAC assistance on Monel technology. NERAC (New England Research Application Center) provided an information package which proved very helpful. The NASA database was included in NERAC's search and yielded a wealth of information on machining Monel.

  2. A Comparison of Molecular Vibrational Theory to Huckel Molecular Orbital Theory.

    ERIC Educational Resources Information Center

    Keeports, David

    1986-01-01

    Compares the similar mathematical problems of molecular vibrational calculations (at any intermediate level of sophistication) and molecular orbital calculations (at the Huckel level). Discusses how the generalizations of Huckel treatment of molecular orbitals apply to vibrational theory. (TW)

  3. Sensorless control for a sophisticated artificial myocardial contraction by using shape memory alloy fibre.

    PubMed

    Shiraishi, Y; Yambe, T; Saijo, Y; Sato, F; Tanaka, A; Yoshizawa, M; Sugai, T K; Sakata, R; Luo, Y; Park, Y; Uematsu, M; Umezu, M; Fujimoto, T; Masumoto, N; Liu, H; Baba, A; Konno, S; Nitta, S; Imachi, K; Tabayashi, K; Sasada, H; Homma, D

    2008-01-01

    The authors have been developing an artificial myocardium, which is capable of supporting natural contractile function from the outside of the ventricle. The system was originally designed by using sophisticated covalent shape memory alloy fibres, and the surface did not implicate blood compatibility. The purpose of our study on the development of artificial myocardium was to achieve the assistance of myocardial functional reproduction by the integrative small mechanical elements without sensors, so that the effective circulatory support could be accomplished. In this study, the authors fabricated the prototype artificial myocardial assist unit composed of the sophisticated shape memory alloy fibre (Biometal), the diameter of which was 100 microns, and examined the mechanical response by using pulse width modulation (PWM) control method in each unit. Prior to the evaluation of dynamic characteristics, the relationship between strain and electric resistance and also the initial response of each unit were obtained. The component for the PWM control was designed in order to regulate the myocardial contractile function, which consisted of an originally-designed RISC microcomputer with the input of displacement, and its output signal was controlled by pulse wave modulation method. As a result, the optimal PWM parameters were confirmed and the fibrous displacement was successfully regulated under the different heat transfer conditions simulating internal body temperature as well as bias tensile loading. Then it was indicated that this control theory might be applied for more sophisticated ventricular passive or active restraint by the artificial myocardium on physiological demand. PMID:19162754

  4. Workout Machine

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Orbotron is a tri-axle exercise machine patterned after a NASA training simulator for astronaut orientation in the microgravity of space. It has three orbiting rings corresponding to roll, pitch and yaw. The user is in the middle of the inner ring with the stomach remaining in the center of all axes, eliminating dizziness. Human power starts the rings spinning, unlike the NASA air-powered system. Marketed by Fantasy Factory (formerly Orbotron, Inc.), the machine can improve aerobic capacity, strength and endurance in five to seven minute workouts.

  5. Wacky Machines

    ERIC Educational Resources Information Center

    Fendrich, Jean

    2002-01-01

    Collectors everywhere know that local antique shops and flea markets are treasure troves just waiting to be plundered. Science teachers might take a hint from these hobbyists, for the next community yard sale might be a repository of old, quirky items that are just the things to get students thinking about simple machines. By introducing some…

  6. Drilling Machines: Vocational Machine Shop.

    ERIC Educational Resources Information Center

    Thomas, John C.

    The lessons and supportive information in this field tested instructional block provide a guide for teachers in developing a machine shop course of study in drilling. The document is comprised of operation sheets, information sheets, and transparency masters for 23 lessons. Each lesson plan includes a performance objective, material and tools,…

  7. Electric Power Demand and Emerging Technology in Highly-sophisticated Electric Power Systems

    NASA Astrophysics Data System (ADS)

    Matsumoto, Satoshi; Hikita, Masayuki

    In the last few years, the increase of the electric power demand has been remarkable, especially in Asia district. In such trend, the electric power system of Japan has been supplied with high quality, high reliability and highly-stabilized electric power. This is supported by highly-sophisticated electric power system which prides oneself on high voltage and large capacity. In this paper, outlines of these technologies are described. And, newest technology trends such as electric power liberalization, innovation of dispersed power source, effective utilization of natural energy are also explained. In addition, the global standards are important to make the technological level of Japan to be the world one in future.

  8. Atwood's Machine as a Tool to Introduce Variable Mass Systems

    ERIC Educational Resources Information Center

    de Sousa, Celia A.

    2012-01-01

    This article discusses an instructional strategy which explores eventual similarities and/or analogies between familiar problems and more sophisticated systems. In this context, the Atwood's machine problem is used to introduce students to more complex problems involving ropes and chains. The methodology proposed helps students to develop the…

  9. Charging machine

    DOEpatents

    Medlin, John B.

    1976-05-25

    A charging machine for loading fuel slugs into the process tubes of a nuclear reactor includes a tubular housing connected to the process tube, a charging trough connected to the other end of the tubular housing, a device for loading the charging trough with a group of fuel slugs, means for equalizing the coolant pressure in the charging trough with the pressure in the process tubes, means for pushing the group of fuel slugs into the process tube and a latch and a seal engaging the last object in the group of fuel slugs to prevent the fuel slugs from being ejected from the process tube when the pusher is removed and to prevent pressure liquid from entering the charging machine.

  10. Induction machine

    DOEpatents

    Owen, Whitney H.

    1980-01-01

    A polyphase rotary induction machine for use as a motor or generator utilizing a single rotor assembly having two series connected sets of rotor windings, a first stator winding disposed around the first rotor winding and means for controlling the current induced in one set of the rotor windings compared to the current induced in the other set of the rotor windings. The rotor windings may be wound rotor windings or squirrel cage windings.

  11. Sophisticated Vegetation Classification Based on Feature Band Set Using Hyperspectral Image.

    PubMed

    Shang, Kun; Zhang, Xia; Sun Yan-li; Zhang, Li-fu; Wang, Shu-dong; Zhuang, Zhi

    2015-06-01

    There are two major problems of sophisticated vegetation classification (SVC) using hyperspectral image. Classification results using only spectral information can hardly meet the application requirements with the needed vegetation type becoming more sophisticated. And applications of classification image are also limited due to salt and pepper noise. Therefore the SVC strategy based on construction and optimization of vegetation feature band set (FBS) is proposed. Besides spectral and texture features of original image, 30 spectral indices which are sensitive to biological parameters of vegetation are added into FBS in order to improve the separability between different kinds of vegetation. And to achieve the same goal a spectral-dimension optimization algorithm of FBS based on class-pair separability (CPS) is also proposed. A spatial-dimension optimization algorithm of FBS based on neighborhood pixels' spectral angle distance (NPSAD) is proposed so that detailed information can be kept during the image smoothing process. The results of SVC experiments based on airborne hyperspectral image show that the proposed method can significantly improve the accuracy of SVC so that some widespread application prospects like identification of crop species, monitoring of invasive species and precision agriculture are expectable. PMID:26601388

  12. Tribology in secondary wood machining

    SciTech Connect

    Ko, P.L.; Hawthorne, H.M.; Andiappan, J.

    1998-07-01

    Secondary wood manufacturing covers a wide range of products from furniture, cabinets, doors and windows, to musical instruments. Many of these are now mass produced in sophisticated, high speed numerical controlled machines. The performance and the reliability of the tools are key to an efficient and economical manufacturing process as well as to the quality of the finished products. A program concerned with three aspects of tribology of wood machining, namely, tool wear, tool-wood friction characteristics and wood surface quality characterization, was set up in the Integrated Manufacturing Technologies Institute (IMTI) of the National Research Council of Canada. The studies include friction and wear mechanism identification and modeling, wear performance of surface-engineered tool materials, friction-induced vibration and cutting efficiency, and the influence of wear and friction on finished products. This research program underlines the importance of tribology in secondary wood manufacturing and at the same time adds new challenges to tribology research since wood is a complex, heterogeneous, material and its behavior during machining is highly sensitive to the surrounding environments and to the moisture content in the work piece.

  13. Electrical machine

    DOEpatents

    De Bock, Hendrik Pieter Jacobus; Alexander, James Pellegrino; El-Refaie, Ayman Mohamed Fawzi; Gerstler, William Dwight; Shah, Manoj Ramprasad; Shen, Xiaochun

    2016-06-21

    An apparatus, such as an electrical machine, is provided. The apparatus can include a rotor defining a rotor bore and a conduit disposed in and extending axially along the rotor bore. The conduit can have an annular conduit body defining a plurality of orifices disposed axially along the conduit and extending through the conduit body. The rotor can have an inner wall that at least partially defines the rotor bore. The orifices can extend through the conduit body along respective orifice directions, and the rotor and conduit can be configured to provide a line of sight along the orifice direction from the respective orifices to the inner wall.

  14. TEMPO machine

    SciTech Connect

    Rohwein, G.J.; Lancaster, K.T.; Lawson, R.N.

    1986-06-01

    TEMPO is a transformer powered megavolt pulse generator with an output pulse of 100 ns duration. The machine was designed for burst mode operation at pulse repetition rates up to 10 Hz with minimum pulse-to-pulse voltage variations. To meet the requirement for pulse duration a nd a 20-..omega.. output impedance within reasonable size constraints, the pulse forming transmission line was designed as two parallel water-insulated, strip-type Blumleins. Stray capacitance and electric fields along the edges of the line elements were controlled by lining the tank with plastic sheet.

  15. A sophisticated mechanism for enabling real-time mobile access to PHR data.

    PubMed

    Koufi, Vassiliki; Malamateniou, Flora; Vassilacopoulos, George

    2013-01-01

    Faced with rapid changes, such as growing complexity in care delivery, health systems nowadays fall short in their ability to translate knowledge into practice. Mobile technology holds enormous potential for transforming healthcare delivery systems which currently involve cumbersome processes that slow down care and decrease rather than improve safety. However, the limited computing, energy and information storage capabilities of mobile devices are hampering their ability to support increasingly sophisticated applications required by certain application fields, such as healthcare. This paper is concerned with a framework which provides ubiquitous mobile access to comprehensive health information at any point of care or decision making in a way that efficient utilization of mobile device resources is achieved. To this end, a cloud-based push messaging mechanism is utilized which draws upon and enhances Google Cloud Messaging service. PMID:23823405

  16. Recent progress of HIMAC for sophisticated heavy-ion cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Noda, K.; Furukawa, T.; Fujimoto, T.; Hara, Y.; Inaniwa, T.; Iwata, Y.; Katagiri, K.; Kanematsu, N.; Mizushima, K.; Miyoshi, T.; Mori, S.; Murakami, T.; Sano, Y.; Sato, S.; Shirai, T.; Takada, E.; Takei, Y.; Yonai, S.

    2014-07-01

    The NIRS has carried out carbon-ion radiotherapy (RT) with HIMAC since 1994. On the basis of their ten-year HIMAC experience, NIRS has developed a standard-type CIRT facility in order to boost availability of carbon-ion RT in Japan. Work has been carried out at its pilot facility at Gunma University since 2010. The current projects of the pilot facility include Saga-HIMAT and i-ROCK, promoted by the Kanagawa prefectural cancer center. Toward the further sophisticated conformal carbon-ion RT with HIMAC, the NIRS has since 2006 been developing new treatment technologies, such as a fast 3D rescanning with a pencil beam and a compact rotating gantry.

  17. When not to copy: female fruit flies use sophisticated public information to avoid mated males

    NASA Astrophysics Data System (ADS)

    Loyau, Adeline; Blanchet, Simon; van Laere, Pauline; Clobert, Jean; Danchin, Etienne

    2012-10-01

    Semen limitation (lack of semen to fertilize all of a female's eggs) imposes high fitness costs to female partners. Females should therefore avoid mating with semen-limited males. This can be achieved by using public information extracted from watching individual males' previous copulating activities. This adaptive preference should be flexible given that semen limitation is temporary. We first demonstrate that the number of offspring produced by males Drosophila melanogaster gradually decreases over successive copulations. We then show that females avoid mating with males they just watched copulating and that visual public cues are sufficient to elicit this response. Finally, after males were given the time to replenish their sperm reserves, females did not avoid the males they previously saw copulating anymore. These results suggest that female fruit flies may have evolved sophisticated behavioural processes of resistance to semen-limited males, and demonstrate unsuspected adaptive context-dependent mate choice in an invertebrate.

  18. AIDS and the rights of the individual: toward a more sophisticated understanding of discrimination.

    PubMed

    Stoddard, Thomas B; Rieman, Walter

    1990-01-01

    AIDS is the first public health crisis in America to arise after the mid-century civil rights revolution. Reflecting the values of the civil rights movement, public health experts have drawn attention to the dangers of discrimination against individuals who are sick or at risk, and generally have expressed a preference for voluntary over compulsory measures to limit the spread of the illness. Remarkably, government officials--judges, legislators, and administrators--have largely acceded to the views of these experts. This perspective indicates a more sophisticated understanding of discrimination issues throughout society; experience with AIDS may itself help to transform and refine ideas about individual rights, especially the constitutional conception of "equal protection under the law." PMID:11650414

  19. Tunneling machine

    SciTech Connect

    Snyder, L.L.

    1980-02-19

    A diametrically compact tunneling machine for boring tunnels is disclosed. The machine includes a tubular support frame having a hollow piston mounted therein which is movable from a retracted position in the support frame to an extended position. A drive shaft is rotatably mounted in the hollow piston and carries a cutter head at one end. The hollow piston is restrained against rotational movement relative to the support frame and the drive shaft is constrained against longitudinal movement relative to the hollow piston. A plurality of radially extendible feet project from the support frame to the tunnel wall to grip the tunnel wall during a tunneling operation wherein the hollow piston is driven forwardly so that the cutter head works on the tunnel face. When the hollow piston is fully extended, a plurality of extendible support feet, which are fixed to the rearward and forward ends of the hollow piston, are extended, the radially extendible feet are retracted and the support frame is shifted forwardly by the piston so that a further tunneling operation may be initiated.

  20. Parallel machines: Parallel machine languages

    SciTech Connect

    Iannucci, R.A. )

    1990-01-01

    This book presents a framework for understanding the tradeoffs between the conventional view and the dataflow view with the objective of discovering the critical hardware structures which must be present in any scalable, general-purpose parallel computer to effectively tolerate latency and synchronization costs. The author presents an approach to scalable general purpose parallel computation. Linguistic Concerns, Compiling Issues, Intermediate Language Issues, and hardware/technological constraints are presented as a combined approach to architectural Develoement. This book presents the notion of a parallel machine language.

  1. Predicting fecal sources in waters with diverse pollution loads using general and molecular host-specific indicators and applying machine learning methods.

    PubMed

    Casanovas-Massana, Arnau; Gómez-Doñate, Marta; Sánchez, David; Belanche-Muñoz, Lluís A; Muniesa, Maite; Blanch, Anicet R

    2015-03-15

    In this study we use a machine learning software (Ichnaea) to generate predictive models for water samples with different concentrations of fecal contamination (point source, moderate and low). We applied several MST methods (host-specific Bacteroides phages, mitochondrial DNA genetic markers, Bifidobacterium adolescentis and Bifidobacterium dentium markers, and bifidobacterial host-specific qPCR), and general indicators (Escherichia coli, enterococci and somatic coliphages) to evaluate the source of contamination in the samples. The results provided data to the Ichnaea software, that evaluated the performance of each method in the different scenarios and determined the source of the contamination. Almost all MST methods in this study determined correctly the origin of fecal contamination at point source and in moderate concentration samples. When the dilution of the fecal pollution increased (below 3 log10 CFU E. coli/100 ml) some of these indicators (bifidobacterial host-specific qPCR, some mitochondrial markers or B. dentium marker) were not suitable because their concentrations decreased below the detection limit. Using the data from source point samples, the software Ichnaea produced models for waters with low levels of fecal pollution. These models included some MST methods, on the basis of their best performance, that were used to determine the source of pollution in this area. Regardless the methods selected, that could vary depending on the scenario, inductive machine learning methods are a promising tool in MST studies and may represent a leap forward in solving MST cases. PMID:25585145

  2. Micro-machined calorimetric biosensors

    DOEpatents

    Doktycz, Mitchel J.; Britton, Jr., Charles L.; Smith, Stephen F.; Oden, Patrick I.; Bryan, William L.; Moore, James A.; Thundat, Thomas G.; Warmack, Robert J.

    2002-01-01

    A method and apparatus are provided for detecting and monitoring micro-volumetric enthalpic changes caused by molecular reactions. Micro-machining techniques are used to create very small thermally isolated masses incorporating temperature-sensitive circuitry. The thermally isolated masses are provided with a molecular layer or coating, and the temperature-sensitive circuitry provides an indication when the molecules of the coating are involved in an enthalpic reaction. The thermally isolated masses may be provided singly or in arrays and, in the latter case, the molecular coatings may differ to provide qualitative and/or quantitative assays of a substance.

  3. Green machining of gelcast ceramic materials

    SciTech Connect

    Nunn, S.D.; Kirby, G.H.

    1996-04-01

    Ceramic green bodies prepared by gelcasting were shown to be readily machinable using WC cutting tools. Samples of alumina and silicon nitride were examined. It was found that a gelcasting formulation which uses a high molecular weight cross-linking agent produces a green body having superior machining characteristics. Samples fabricated with a lower molecular weight cross-linker exhibited a poor machined surface finish due to chipping. Machining tests showed that using a 3.2 mm (0.125 in.) diameter cutting tool at a cutting speed of 162.5 cm/sec (64 ft./sec.) to machine a flat-bottomed groove 3.2 mm wide and 9.5 mm deep (0.125 x 0.375 in.) using three passes, feed rates ranging from 0.85 to 6.35 cm/sec (0.33 to 2.50 in./sec.) could be used without damaging the sample.

  4. Sophisticated test objects for the quality assurance of optical computed tomography scanners

    NASA Astrophysics Data System (ADS)

    Rahman, A. T. Abdul; Bräuer-Krisch, Elke; Brochard, Thierry; Adamovics, John; Clowes, S. K.; Bradley, David; Doran, Simon J.

    2011-07-01

    Optical computed tomography (CT), in conjunction with radiochromic gels and plastics, shows great potential for radiation therapy dose verification in 3D. However, an effective quality assurance (QA) regime for the various scanners currently available still remains to be developed. We show how the favourable properties of the PRESAGE® radiochromic polymer may be exploited to create highly sophisticated QA phantoms. Five 60 mm diameter cylindrical PRESAGE® samples were irradiated using the x-ray microbeam radiation therapy facility on the ID-17 biomedical beamline at the European Synchrotron Radiation Facility. Samples were then imaged on the University of Surrey parallel-beam optical CT scanner. The sample irradiations were designed to allow a variety of tests to be performed, including assessments of linearity, modulation transfer function (three independent measurements), geometric distortion and the effect of treatment fractionation. It is clear that, although the synchrotron method produces extremely high-quality test objects, it is not practical on a routine basis, because of its reliance on a highly specialized radiation source. Hence, we investigated a second possibility: three PRESAGE® samples were illuminated with ultraviolet light of wavelength 365 nm, using cheap masks created by laser-printing patterns onto overhead projector acetate sheets. There was good correlation between optical densities measured by the CT scanner and the expected UV 'dose' delivered. The results are encouraging and a proposal is made for a scanner test regime based on calibrated and well-characterized PRESAGE® samples.

  5. Yersinia virulence factors - a sophisticated arsenal for combating host defences.

    PubMed

    Atkinson, Steve; Williams, Paul

    2016-01-01

    The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six 'effector' proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen. PMID:27347390

  6. A sophisticated, multi-channel data acquisition and processing system for high frequency noise research

    NASA Technical Reports Server (NTRS)

    Hall, David G.; Bridges, James

    1992-01-01

    A sophisticated, multi-channel computerized data acquisition and processing system was developed at the NASA LeRC for use in noise experiments. This technology, which is available for transfer to industry, provides a convenient, cost-effective alternative to analog tape recording for high frequency acoustic measurements. This system provides 32-channel acquisition of microphone signals with an analysis bandwidth up to 100 kHz per channel. Cost was minimized through the use of off-the-shelf components. Requirements to allow for future expansion were met by choosing equipment which adheres to established industry standards for hardware and software. Data processing capabilities include narrow band and 1/3 octave spectral analysis, compensation for microphone frequency response/directivity, and correction of acoustic data to standard day conditions. The system was used successfully in a major wind tunnel test program at NASA LeRC to acquire and analyze jet noise data in support of the High Speed Civil Transport (HSCT) program.

  7. Simple Plans or Sophisticated Habits? State, Transition and Learning Interactions in the Two-Step Task.

    PubMed

    Akam, Thomas; Costa, Rui; Dayan, Peter

    2015-12-01

    The recently developed 'two-step' behavioural task promises to differentiate model-based from model-free reinforcement learning, while generating neurophysiologically-friendly decision datasets with parametric variation of decision variables. These desirable features have prompted its widespread adoption. Here, we analyse the interactions between a range of different strategies and the structure of transitions and outcomes in order to examine constraints on what can be learned from behavioural performance. The task involves a trade-off between the need for stochasticity, to allow strategies to be discriminated, and a need for determinism, so that it is worth subjects' investment of effort to exploit the contingencies optimally. We show through simulation that under certain conditions model-free strategies can masquerade as being model-based. We first show that seemingly innocuous modifications to the task structure can induce correlations between action values at the start of the trial and the subsequent trial events in such a way that analysis based on comparing successive trials can lead to erroneous conclusions. We confirm the power of a suggested correction to the analysis that can alleviate this problem. We then consider model-free reinforcement learning strategies that exploit correlations between where rewards are obtained and which actions have high expected value. These generate behaviour that appears model-based under these, and also more sophisticated, analyses. Exploiting the full potential of the two-step task as a tool for behavioural neuroscience requires an understanding of these issues. PMID:26657806

  8. The Virtual ChemLab Project: A Realistic and Sophisticated Simulation of Inorganic Qualitative Analysis

    NASA Astrophysics Data System (ADS)

    Woodfield, Brian F.; Catlin, Heidi R.; Waddoups, Gregory L.; Moore, Melissa S.; Swan, Richard; Allen, Rob; Bodily, Greg

    2004-11-01

    We have created a set of sophisticated and realistic laboratory simulations for use in freshman- and sophomore-level chemistry classes and laboratories called Virtual ChemLab. We have completed simulations for Inorganic Qualitative Analysis, Organic Synthesis and Organic Qualitative Analysis, Experiments in Quantum Chemistry, Gas Properties, Titration Experiments, and Calorimetric and Thermochemical Experiments. The purpose of our simulations is to reinforce concepts taught in the classroom, provide an environment for creative learning, and emphasize the thinking behind instructional laboratory experiments. We have used the inorganic simulation extensively with thousands of students in our department at Brigham Young University. We have learned from our evaluation that: (i) students enjoy using these simulations and find them to be an asset in learning effective problem-solving strategies, (ii) students like the fact that they can both reproduce experimental procedures and explore various topics in ways they choose, and (iii) students naturally divide themselves into two groups: creative learners, who excel in an open-ended environment of virtual laboratories, and structured learners, who struggle in this same environment. In this article, we describe the Inorganic Qualitative Analysis simulation; we also share specific evaluation findings from using the inorganic simulation in classroom and laboratory settings.

  9. The Impact of Services on Economic Complexity: Service Sophistication as Route for Economic Growth

    PubMed Central

    Utkovski, Zoran; Kocarev, Ljupco

    2016-01-01

    Economic complexity reflects the amount of knowledge that is embedded in the productive structure of an economy. By combining tools from network science and econometrics, a robust and stable relationship between a country’s productive structure and its economic growth has been established. Here we report that not only goods but also services are important for predicting the rate at which countries will grow. By adopting a terminology which classifies manufactured goods and delivered services as products, we investigate the influence of services on the country’s productive structure. In particular, we provide evidence that complexity indices for services are in general higher than those for goods, which is reflected in a general tendency to rank countries with developed service sector higher than countries with economy centred on manufacturing of goods. By focusing on country dynamics based on experimental data, we investigate the impact of services on the economic complexity of countries measured in the product space (consisting of both goods and services). Importantly, we show that diversification of service exports and its sophistication can provide an additional route for economic growth in both developing and developed countries. PMID:27560133

  10. Yersinia virulence factors - a sophisticated arsenal for combating host defences

    PubMed Central

    Atkinson, Steve; Williams, Paul

    2016-01-01

    The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen. PMID:27347390

  11. The Impact of Services on Economic Complexity: Service Sophistication as Route for Economic Growth.

    PubMed

    Stojkoski, Viktor; Utkovski, Zoran; Kocarev, Ljupco

    2016-01-01

    Economic complexity reflects the amount of knowledge that is embedded in the productive structure of an economy. By combining tools from network science and econometrics, a robust and stable relationship between a country's productive structure and its economic growth has been established. Here we report that not only goods but also services are important for predicting the rate at which countries will grow. By adopting a terminology which classifies manufactured goods and delivered services as products, we investigate the influence of services on the country's productive structure. In particular, we provide evidence that complexity indices for services are in general higher than those for goods, which is reflected in a general tendency to rank countries with developed service sector higher than countries with economy centred on manufacturing of goods. By focusing on country dynamics based on experimental data, we investigate the impact of services on the economic complexity of countries measured in the product space (consisting of both goods and services). Importantly, we show that diversification of service exports and its sophistication can provide an additional route for economic growth in both developing and developed countries. PMID:27560133

  12. Simple Plans or Sophisticated Habits? State, Transition and Learning Interactions in the Two-Step Task

    PubMed Central

    Akam, Thomas; Costa, Rui; Dayan, Peter

    2015-01-01

    The recently developed ‘two-step’ behavioural task promises to differentiate model-based from model-free reinforcement learning, while generating neurophysiologically-friendly decision datasets with parametric variation of decision variables. These desirable features have prompted its widespread adoption. Here, we analyse the interactions between a range of different strategies and the structure of transitions and outcomes in order to examine constraints on what can be learned from behavioural performance. The task involves a trade-off between the need for stochasticity, to allow strategies to be discriminated, and a need for determinism, so that it is worth subjects’ investment of effort to exploit the contingencies optimally. We show through simulation that under certain conditions model-free strategies can masquerade as being model-based. We first show that seemingly innocuous modifications to the task structure can induce correlations between action values at the start of the trial and the subsequent trial events in such a way that analysis based on comparing successive trials can lead to erroneous conclusions. We confirm the power of a suggested correction to the analysis that can alleviate this problem. We then consider model-free reinforcement learning strategies that exploit correlations between where rewards are obtained and which actions have high expected value. These generate behaviour that appears model-based under these, and also more sophisticated, analyses. Exploiting the full potential of the two-step task as a tool for behavioural neuroscience requires an understanding of these issues. PMID:26657806

  13. Machine wanting.

    PubMed

    McShea, Daniel W

    2013-12-01

    Wants, preferences, and cares are physical things or events, not ideas or propositions, and therefore no chain of pure logic can conclude with a want, preference, or care. It follows that no pure-logic machine will ever want, prefer, or care. And its behavior will never be driven in the way that deliberate human behavior is driven, in other words, it will not be motivated or goal directed. Therefore, if we want to simulate human-style interactions with the world, we will need to first understand the physical structure of goal-directed systems. I argue that all such systems share a common nested structure, consisting of a smaller entity that moves within and is driven by a larger field that contains it. In such systems, the smaller contained entity is directed by the field, but also moves to some degree independently of it, allowing the entity to deviate and return, to show the plasticity and persistence that is characteristic of goal direction. If all this is right, then human want-driven behavior probably involves a behavior-generating mechanism that is contained within a neural field of some kind. In principle, for goal directedness generally, the containment can be virtual, raising the possibility that want-driven behavior could be simulated in standard computational systems. But there are also reasons to believe that goal-direction works better when containment is also physical, suggesting that a new kind of hardware may be necessary. PMID:23792091

  14. Machine musicianship

    NASA Astrophysics Data System (ADS)

    Rowe, Robert

    2002-05-01

    The training of musicians begins by teaching basic musical concepts, a collection of knowledge commonly known as musicianship. Computer programs designed to implement musical skills (e.g., to make sense of what they hear, perform music expressively, or compose convincing pieces) can similarly benefit from access to a fundamental level of musicianship. Recent research in music cognition, artificial intelligence, and music theory has produced a repertoire of techniques that can make the behavior of computer programs more musical. Many of these were presented in a recently published book/CD-ROM entitled Machine Musicianship. For use in interactive music systems, we are interested in those which are fast enough to run in real time and that need only make reference to the material as it appears in sequence. This talk will review several applications that are able to identify the tonal center of musical material during performance. Beyond this specific task, the design of real-time algorithmic listening through the concurrent operation of several connected analyzers is examined. The presentation includes discussion of a library of C++ objects that can be combined to perform interactive listening and a demonstration of their capability.

  15. The sophisticated visual system of a tiny Cambrian crustacean: analysis of a stalked fossil compound eye.

    PubMed

    Schoenemann, Brigitte; Castellani, Christopher; Clarkson, Euan N K; Haug, Joachim T; Maas, Andreas; Haug, Carolin; Waloszek, Dieter

    2012-04-01

    Fossilized compound eyes from the Cambrian, isolated and three-dimensionally preserved, provide remarkable insights into the lifestyle and habitat of their owners. The tiny stalked compound eyes described here probably possessed too few facets to form a proper image, but they represent a sophisticated system for detecting moving objects. The eyes are preserved as almost solid, mace-shaped blocks of phosphate, in which the original positions of the rhabdoms in one specimen are retained as deep cavities. Analysis of the optical axes reveals four visual areas, each with different properties in acuity of vision. They are surveyed by lenses directed forwards, laterally, backwards and inwards, respectively. The most intriguing of these is the putatively inwardly orientated zone, where the optical axes, like those orientated to the front, interfere with axes of the other eye of the contralateral side. The result is a three-dimensional visual net that covers not only the front, but extends also far laterally to either side. Thus, a moving object could be perceived by a two-dimensional coordinate (which is formed by two axes of those facets, one of the left and one of the right eye, which are orientated towards the moving object) in a wide three-dimensional space. This compound eye system enables small arthropods equipped with an eye of low acuity to estimate velocity, size or distance of possible food items efficiently. The eyes are interpreted as having been derived from individuals of the early crustacean Henningsmoenicaris scutula pointing to the existence of highly efficiently developed eyes in the early evolutionary lineage leading towards the modern Crustacea. PMID:22048954

  16. Nitrogen removal during leachate treatment: comparison of simple and sophisticated systems.

    PubMed

    Vasel, J L; Jupsin, H; Annachhatre, A P

    2004-01-01

    Membrane bioreactors (MBR) have become common in treating municipal wastewaters. Applied to leachates treatment MBR were also successful with pilot scale experiments and full-scale facilities as well. We succeeded previously in designing an efficient nitrification-denitrification process with an ethylene glycol byproduct as carbon source for denitrification. Moreover, an unexpectedly high inert COD removal efficiency was also observed in the full-scale MBR facility thereby making it possible to increase the operating time of the final GAC (Granulated Activated Carbon) adsorber. Since MBR are very sophisticated systems. Simpler and "lower" cost systems can also be considered. For example it is possible to nitrify leachates from sanitary landfill using a simple infiltration-percolation technique with a low energy cost. To validate previously published laboratory experiments, a semi industrial-scale pilot installation was installed at the Montzen landfill site (Belgium). The process is based on infiltration-percolation through a granular bed. This well known process was modified to increase the load, notably by changing the support medium, adding an electric fan that is run intermittently and maintaining temperatures greater than 15 degrees C. The new material is a type of granular calcium carbonate with a large specific surface area. These technical improvements enabled the system to nitrify up to 0.4 kg NH4+-N/m3 of reactor bed per day at a hydraulic load of 0.35 m.d(-1), with an ammonia removal rate in the range of 80 to 95%. Despite the high ammonia nitrogen inlet concentrations, this system exhibits remarkable nitrification efficiency. Moreover, these performances are achieved in a batch mode system without recirculation or dilution processes. If complete nitrification is needed, it can be obtained in a second in series of bioreactors. The system can be classified as a low cost process. An international patent is pending. Possible performances of those systems

  17. Sophisticated oil film geometries through incomplete electrical dewetting by feedback control and Fourier construction.

    PubMed

    Hsieh, Wan-Lin; Chen, Kuo-Ching; Heikenfeld, Jason

    2015-06-21

    Existing techniques for electronic control of the interface between two immiscible fluids are typically limited to simple periodic geometries (symmetric waves) or spherical geometries (only two principle radii of curvature). Presented here, is a new technique with much more sophisticated electronic control of fluid meniscus geometry. Previously undemonstrated two-fluid interfaces, such as asymmetric saw-tooth profiles, are created by dynamic modulation of an incomplete dewetting state for an oil film covering an array of control electrodes, with the oil film itself covered by an electrically conductive fluid acting as the ground electrode. Two distinct approaches are demonstrated: (1) application of voltages, electrical capacitance sensing of meniscus geometry, followed by further feedback control of the applied voltages based on the sensed electrical capacitance; (2) use of multiple periodic voltage waveforms and wave propagation across the meniscus to build up complex meniscus geometries by Fourier construction. These approaches are demonstrated in this work by a proven electro-hydrodynamic modeling method, which couples the Maxwell stress tensor with the laminar phase field of the oil-water dual phase. This work could serve numerous applications including particle or fluid transport (e.g. lab-on-chip), or adaptive optical surfaces (e.g. liquid prism arrays). Importantly, the results can be achieved using conventional materials, and the fluids respond with speeds that are adequately slow (ms-μs) such that even conventional control electronics (μs-ns) are more than adequate. Furthermore, because the conducting fluid never dewets the oil film from the solid surface, dielectric degradation issues are likely eliminated. PMID:25978122

  18. Increasing signal processing sophistication in the calculation of the respiratory modulation of the photoplethysmogram (DPOP).

    PubMed

    Addison, Paul S; Wang, Rui; Uribe, Alberto A; Bergese, Sergio D

    2015-06-01

    DPOP (∆POP or Delta-POP) is a non-invasive parameter which measures the strength of respiratory modulations present in the pulse oximetry photoplethysmogram (pleth) waveform. It has been proposed as a non-invasive surrogate parameter for pulse pressure variation (PPV) used in the prediction of the response to volume expansion in hypovolemic patients. Many groups have reported on the DPOP parameter and its correlation with PPV using various semi-automated algorithmic implementations. The study reported here demonstrates the performance gains made by adding increasingly sophisticated signal processing components to a fully automated DPOP algorithm. A DPOP algorithm was coded and its performance systematically enhanced through a series of code module alterations and additions. Each algorithm iteration was tested on data from 20 mechanically ventilated OR patients. Correlation coefficients and ROC curve statistics were computed at each stage. For the purposes of the analysis we split the data into a manually selected 'stable' region subset of the data containing relatively noise free segments and a 'global' set incorporating the whole data record. Performance gains were measured in terms of correlation against PPV measurements in OR patients undergoing controlled mechanical ventilation. Through increasingly advanced pre-processing and post-processing enhancements to the algorithm, the correlation coefficient between DPOP and PPV improved from a baseline value of R = 0.347 to R = 0.852 for the stable data set, and, correspondingly, R = 0.225 to R = 0.728 for the more challenging global data set. Marked gains in algorithm performance are achievable for manually selected stable regions of the signals using relatively simple algorithm enhancements. Significant additional algorithm enhancements, including a correction for low perfusion values, were required before similar gains were realised for the more challenging global data set. PMID:25209132

  19. On the relevance of sophisticated structural annotations for disulfide connectivity pattern prediction.

    PubMed

    Becker, Julien; Maes, Francis; Wehenkel, Louis

    2013-01-01

    Disulfide bridges strongly constrain the native structure of many proteins and predicting their formation is therefore a key sub-problem of protein structure and function inference. Most recently proposed approaches for this prediction problem adopt the following pipeline: first they enrich the primary sequence with structural annotations, second they apply a binary classifier to each candidate pair of cysteines to predict disulfide bonding probabilities and finally, they use a maximum weight graph matching algorithm to derive the predicted disulfide connectivity pattern of a protein. In this paper, we adopt this three step pipeline and propose an extensive study of the relevance of various structural annotations and feature encodings. In particular, we consider five kinds of structural annotations, among which three are novel in the context of disulfide bridge prediction. So as to be usable by machine learning algorithms, these annotations must be encoded into features. For this purpose, we propose four different feature encodings based on local windows and on different kinds of histograms. The combination of structural annotations with these possible encodings leads to a large number of possible feature functions. In order to identify a minimal subset of relevant feature functions among those, we propose an efficient and interpretable feature function selection scheme, designed so as to avoid any form of overfitting. We apply this scheme on top of three supervised learning algorithms: k-nearest neighbors, support vector machines and extremely randomized trees. Our results indicate that the use of only the PSSM (position-specific scoring matrix) together with the CSP (cysteine separation profile) are sufficient to construct a high performance disulfide pattern predictor and that extremely randomized trees reach a disulfide pattern prediction accuracy of [Formula: see text] on the benchmark dataset SPX[Formula: see text], which corresponds to [Formula: see text

  20. On the Relevance of Sophisticated Structural Annotations for Disulfide Connectivity Pattern Prediction

    PubMed Central

    Becker, Julien; Maes, Francis; Wehenkel, Louis

    2013-01-01

    Disulfide bridges strongly constrain the native structure of many proteins and predicting their formation is therefore a key sub-problem of protein structure and function inference. Most recently proposed approaches for this prediction problem adopt the following pipeline: first they enrich the primary sequence with structural annotations, second they apply a binary classifier to each candidate pair of cysteines to predict disulfide bonding probabilities and finally, they use a maximum weight graph matching algorithm to derive the predicted disulfide connectivity pattern of a protein. In this paper, we adopt this three step pipeline and propose an extensive study of the relevance of various structural annotations and feature encodings. In particular, we consider five kinds of structural annotations, among which three are novel in the context of disulfide bridge prediction. So as to be usable by machine learning algorithms, these annotations must be encoded into features. For this purpose, we propose four different feature encodings based on local windows and on different kinds of histograms. The combination of structural annotations with these possible encodings leads to a large number of possible feature functions. In order to identify a minimal subset of relevant feature functions among those, we propose an efficient and interpretable feature function selection scheme, designed so as to avoid any form of overfitting. We apply this scheme on top of three supervised learning algorithms: k-nearest neighbors, support vector machines and extremely randomized trees. Our results indicate that the use of only the PSSM (position-specific scoring matrix) together with the CSP (cysteine separation profile) are sufficient to construct a high performance disulfide pattern predictor and that extremely randomized trees reach a disulfide pattern prediction accuracy of on the benchmark dataset SPX, which corresponds to improvement over the state of the art. A web-application is

  1. Modeling of cumulative tool wear in machining metal matrix composites

    SciTech Connect

    Hung, N.P.; Tan, V.K.; Oon, B.E.

    1995-12-31

    Metal matrix composites (MMCs) are notoriously known for their low machinability because of the abrasive and brittle reinforcement. Although a near-net-shape product could be produced, finish machining is still required for the final shape and dimension. The classical Taylor`s tool life equation that relates tool life and cutting conditions has been traditionally used to study machinability. The turning operation is commonly used to investigate the machinability of a material; tedious and costly milling experiments have to be performed separately; while a facing test is not applicable for the Taylor`s model since the facing speed varies as the tool moves radially. Collecting intensive machining data for MMCs is often difficult because of the constraints on size, cost of the material, and the availability of sophisticated machine tools. A more flexible model and machinability testing technique are, therefore, sought. This study presents and verifies new models for turning, facing, and milling operations. Different cutting conditions were utilized to assess the machinability of MMCs reinforced with silicon carbide or alumina particles. Experimental data show that tool wear does not depend on the order of different cutting speeds since abrasion is the main wear mechanism. Correlation between data for turning, milling, and facing is presented. It is more economical to rank machinability using data for facing and then to convert the data for turning and milling, if required. Subsurface damages such as work-hardened and cracked matrix alloy, and fractured and delaminated particles are discussed.

  2. Applied machine vision

    SciTech Connect

    Not Available

    1984-01-01

    This book presents the papers given at a conference on robot vision. Topics considered at the conference included the link between fixed and flexible automation, general applications of machine vision, the development of a specification for a machine vision system, machine vision technology, machine vision non-contact gaging, and vision in electronics manufacturing.

  3. Machine Shop Lathes.

    ERIC Educational Resources Information Center

    Dunn, James

    This guide, the second in a series of five machine shop curriculum manuals, was designed for use in machine shop courses in Oklahoma. The purpose of the manual is to equip students with basic knowledge and skills that will enable them to enter the machine trade at the machine-operator level. The curriculum is designed so that it can be used in…

  4. A sophisticated network of signaling pathways regulates stomatal defenses to bacterial pathogens.

    PubMed

    Arnaud, Dominique; Hwang, Ildoo

    2015-04-01

    Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to play an important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns (PAMPs) and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species, nitric oxide, and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine. PMID:25661059

  5. The "Virtual ChemLab" Project: A Realistic and Sophisticated Simulation of Organic Synthesis and Organic Qualitative Analysis

    ERIC Educational Resources Information Center

    Woodfield, Brian F.; Andrus, Merritt B.; Waddoups, Gregory L.; Moore, Melissa S.; Swan, Richard; Allen, Rob; Bodily, Greg; Andersen, Tricia; Miller, Jordan; Simmons, Bryon; Stanger, Richard

    2005-01-01

    A set of sophisticated and realistic laboratory simulations is created for use in freshman- and sophomore-level chemistry classes and laboratories called 'Virtual ChemLab'. A detailed assessment of student responses is provided and the simulation's pedagogical utility is described using the organic simulation.

  6. Increasing the Pedagogical Sophistication of Parents: The Basis for Improving the Education of School Pupils in the Family Setting

    ERIC Educational Resources Information Center

    Grebennikov, I. V.

    1978-01-01

    Maintains that lack of pedagogical training of parents in the Soviet Union leads to errors in the education of children in the family setting. Methods to increase parents' pedagogical sophistication include media presentations about social education, community education clubs for young families, parent teacher conferences, and training sessions…

  7. Aspects of Lexical Sophistication in Advanced Learners' Oral Production: Vocabulary Acquisition and Use in L2 French and Italian

    ERIC Educational Resources Information Center

    Bardel, Camilla; Gudmundson, Anna; Lindqvist, Christina

    2012-01-01

    This article reports on the design and use of a profiler for lexical sophistication (i.e., use of advanced vocabulary), which was created to assess the lexical richness of intermediate and advanced Swedish second language (L2) learners' French and Italian. It discusses how teachers' judgments (TJs) of word difficulty can contribute to the…

  8. Synthetic recombinase-based state machines in living cells.

    PubMed

    Roquet, Nathaniel; Soleimany, Ava P; Ferris, Alyssa C; Aaronson, Scott; Lu, Timothy K

    2016-07-22

    State machines underlie the sophisticated functionality behind human-made and natural computing systems that perform order-dependent information processing. We developed a recombinase-based framework for building state machines in living cells by leveraging chemically controlled DNA excision and inversion operations to encode states in DNA sequences. This strategy enables convenient readout of states (by sequencing and/or polymerase chain reaction) as well as complex regulation of gene expression. We validated our framework by engineering state machines in Escherichia coli that used one, two, or three chemical inputs to control up to 16 DNA states. These state machines were capable of recording the temporal order of all inputs and performing multi-input, multi-output control of gene expression. We also developed a computational tool for the automated design of gene regulation programs using recombinase-based state machines. Our scalable framework should enable new strategies for recording and studying how combinational and temporal events regulate complex cell functions and for programming sophisticated cell behaviors. PMID:27463678

  9. TH-C-17A-06: A Hardware Implementation and Evaluation of Robotic SPECT: Toward Molecular Imaging Onboard Radiation Therapy Machines

    SciTech Connect

    Yan, S; Touch, M; Bowsher, J; Yin, F; Cheng, L

    2014-06-15

    Purpose: To construct a robotic SPECT system and demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch. The system has potential for on-board functional and molecular imaging in radiation therapy. Methods: A robotic SPECT imaging system was developed utilizing a Digirad 2020tc detector and a KUKA KR150-L110 robot. An imaging study was performed with the PET CT Phantom, which includes 5 spheres: 10, 13, 17, 22 and 28 mm in diameter. Sphere-tobackground concentration ratio was 6:1 of Tc99m. The phantom was placed on a flat-top couch. SPECT projections were acquired with a parallel-hole collimator and a single pinhole collimator. The robotic system navigated the detector tracing the flat-top table to maintain the closest possible proximity to the phantom. For image reconstruction, detector trajectories were described by six parameters: radius-of-rotation, x and z detector shifts, and detector rotation θ, tilt ϕ and twist γ. These six parameters were obtained from the robotic system by calibrating the robot base and tool coordinates. Results: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector-to-COR (center-ofrotation) distance. In acquisitions with background at 1/6th sphere activity concentration, photopeak contamination was heavy, yet the 17, 22, and 28 mm diameter spheres were readily observed with the parallel hole imaging, and the single, targeted sphere (28 mm diameter) was readily observed in the pinhole region-of-interest (ROI) imaging. Conclusion: Onboard SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frame could be an effective means to estimate detector pose for use in SPECT image reconstruction. PHS/NIH/NCI grant R21-CA156390-01A1.

  10. Hard Machinable Machining of Cobalt Super Alloys

    NASA Astrophysics Data System (ADS)

    Čep, Robert; Janásek, Adam; Petrů, Jana; Čepová, Lenka; Sadílek, Marek; Kratochvíl, Jiří

    2012-12-01

    The article deals with difficult-to-machine cobalt super alloys. The main aim is to test the basic properties of cobalt super alloys and propose suitable cutting materials and machining parameters under the designation 188 when machining. Although the development of technology in chipless machining such as moulding, precision casting and other manufacturing methods continues to advance, machining is still the leading choice for piece production, typical for energy and chemical engineering. Nowadays, super alloys are commonly used in turbine engines in regions that are subject to high temperatures, which require high strength, high temperature resistance, phase stability, as well as corrosion or oxidation resistance.

  11. Women, Men, and Machines.

    ERIC Educational Resources Information Center

    Form, William; McMillen, David Byron

    1983-01-01

    Data from the first national study of technological change show that proportionately more women than men operate machines, are more exposed to machines that have alienating effects, and suffer more from the negative effects of technological change. (Author/SSH)

  12. Tube Alinement for Machining

    NASA Technical Reports Server (NTRS)

    Garcia, J.

    1984-01-01

    Tool with stepped shoulders alines tubes for machining in preparation for welding. Alinement with machine tool axis accurate to within 5 mils (0.13mm) and completed much faster than visual setup by machinist.

  13. Stirling machine operating experience

    NASA Technical Reports Server (NTRS)

    Ross, Brad; Dudenhoefer, James E.

    1991-01-01

    Numerous Stirling machines have been built and operated, but the operating experience of these machines is not well known. It is important to examine this operating experience in detail, because it largely substantiates the claim that Stirling machines are capable of reliable and lengthy lives. The amount of data that exists is impressive, considering that many of the machines that have been built are developmental machines intended to show proof of concept, and were not expected to operate for any lengthy period of time. Some Stirling machines (typically free-piston machines) achieve long life through non-contact bearings, while other Stirling machines (typically kinematic) have achieved long operating lives through regular seal and bearing replacements. In addition to engine and system testing, life testing of critical components is also considered.

  14. A Sophisticated Architecture Is Indeed Necessary for the Implementation of Health in All Policies but not Enough

    PubMed Central

    Breton, Eric

    2016-01-01

    In this commentary, I argue that beyond a sophisticated supportive architecture to facilitate implementation of actions on the social determinants of health (SDOH) and health inequities, the Health in All Policies (HiAP) project faces two main barriers: lack of awareness within policy networks on the social determinants of population health, and a tendency of health actors to neglect investing in other sectors’ complex problems. PMID:27285517

  15. Automatic Inspection During Machining

    NASA Technical Reports Server (NTRS)

    Ransom, Clyde L.

    1988-01-01

    In experimental manufacturing process, numerically-controlled machine tool temporarily converts into inspection machine by installing electronic touch probes and specially-developed numerical-control software. Software drives probes in paths to and on newly machined parts and collects data on dimensions of parts.

  16. Machining lead wafers

    SciTech Connect

    Schamaun, R.T.

    1987-09-01

    Recently, MEC-6 machined some 4-inch-diameter lead wafers to precision tolerances. The tolerance on the wafer thickness was +-0.000080 inch. A diamond tool was used to machine the wafers on a Moore No. 3 lathe. This report discusses the methods used to machine the wafers, the fixtures used to hold the wafers, and the inspection methods and results.

  17. Apprentice Machine Theory Outline.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford. Div. of Vocational-Technical Schools.

    This volume contains outlines for 16 courses in machine theory that are designed for machine tool apprentices. Addressed in the individual course outlines are the following topics: basic concepts; lathes; milling machines; drills, saws, and shapers; heat treatment and metallurgy; grinders; quality control; hydraulics and pneumatics;…

  18. Molecular motors

    NASA Astrophysics Data System (ADS)

    Allemand, Jean François Desbiolles, Pierre

    2015-10-01

    How do we move? More precisely, what are the molecular mechanisms that can explain that our muscles, made of very small components can move at a osopic scale? To answer these questions we must introduce molecular motors. Those motors are proteins, or small protein assemblies that, in our cells, transform chemical energy into mechanical work. Then, like we could do for a oscopic motor, used in a car or in a fan, we are going to study the basic behavior of these molecular machines, present what are their energy sources, calculate their power, their yield. If molecular motors are crucial for our oscopic movements, we are going to see that they are also essential to cellular transport and that considering the activity of some enzymes as molecular motors bring some interesting new insights on their activity.

  19. The bacteriophage DNA packaging machine.

    PubMed

    Feiss, Michael; Rao, Venigalla B

    2012-01-01

    Large dsDNA bacteriophages and herpesviruses encode a powerful ATP-driven DNA-translocating machine that encapsidates a viral genome into a preformed capsid shell or prohead. The key components of the packaging machine are the packaging enzyme (terminase, motor) and the portal protein that forms the unique DNA entrance vertex of prohead. The terminase complex, comprised of a recognition subunit (small terminase) and an endonuclease/translocase subunit (large terminase), cuts viral genome concatemers. The terminase-viral DNA complex docks on the portal vertex, assembling a motor complex containing five large terminase subunits. The pentameric motor processively translocates DNA until the head shell is full with one viral genome. The motor cuts the DNA again and dissociates from the full head, allowing head-finishing proteins to assemble on the portal, sealing the portal, and constructing a platform for tail attachment. A body of evidence from molecular genetics and biochemical, structural, and biophysical approaches suggests that ATP hydrolysis-driven conformational changes in the packaging motor (large terminase) power DNA motion. Various parts of the motor subunit, such as the ATPase, arginine finger, transmission domain, hinge, and DNA groove, work in concert to translocate about 2 bp of DNA per ATP hydrolyzed. Powerful single-molecule approaches are providing precise delineation of steps during each translocation event in a motor that has a speed as high as a millisecond/step. The phage packaging machine has emerged as an excellent model for understanding the molecular machines, given the mechanistic parallels between terminases, helicases, and numerous motor proteins. PMID:22297528

  20. Perspex machine: VII. The universal perspex machine

    NASA Astrophysics Data System (ADS)

    Anderson, James A. D. W.

    2006-01-01

    The perspex machine arose from the unification of projective geometry with the Turing machine. It uses a total arithmetic, called transreal arithmetic, that contains real arithmetic and allows division by zero. Transreal arithmetic is redefined here. The new arithmetic has both a positive and a negative infinity which lie at the extremes of the number line, and a number nullity that lies off the number line. We prove that nullity, 0/0, is a number. Hence a number may have one of four signs: negative, zero, positive, or nullity. It is, therefore, impossible to encode the sign of a number in one bit, as floating-point arithmetic attempts to do, resulting in the difficulty of having both positive and negative zeros and NaNs. Transrational arithmetic is consistent with Cantor arithmetic. In an extension to real arithmetic, the product of zero, an infinity, or nullity with its reciprocal is nullity, not unity. This avoids the usual contradictions that follow from allowing division by zero. Transreal arithmetic has a fixed algebraic structure and does not admit options as IEEE, floating-point arithmetic does. Most significantly, nullity has a simple semantics that is related to zero. Zero means "no value" and nullity means "no information." We argue that nullity is as useful to a manufactured computer as zero is to a human computer. The perspex machine is intended to offer one solution to the mind-body problem by showing how the computable aspects of mind and, perhaps, the whole of mind relates to the geometrical aspects of body and, perhaps, the whole of body. We review some of Turing's writings and show that he held the view that his machine has spatial properties. In particular, that it has the property of being a 7D lattice of compact spaces. Thus, we read Turing as believing that his machine relates computation to geometrical bodies. We simplify the perspex machine by substituting an augmented Euclidean geometry for projective geometry. This leads to a general

  1. Machine Phase Fullerene Nanotechnology: 1996

    NASA Technical Reports Server (NTRS)

    Globus, Al; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    NASA has used exotic materials for spacecraft and experimental aircraft to good effect for many decades. In spite of many advances, transportation to space still costs about $10,000 per pound. Drexler has proposed a hypothetical nanotechnology based on diamond and investigated the properties of such molecular systems. These studies and others suggest enormous potential for aerospace systems. Unfortunately, methods to realize diamonoid nanotechnology are at best highly speculative. Recent computational efforts at NASA Ames Research Center and computation and experiment elsewhere suggest that a nanotechnology of machine phase functionalized fullerenes may be synthetically relatively accessible and of great aerospace interest. Machine phase materials are (hypothetical) materials consisting entirely or in large part of microscopic machines. In a sense, most living matter fits this definition. To begin investigation of fullerene nanotechnology, we used molecular dynamics to study the properties of carbon nanotube based gears and gear/shaft configurations. Experiments on C60 and quantum calculations suggest that benzyne may react with carbon nanotubes to form gear teeth. Han has computationally demonstrated that molecular gears fashioned from (14,0) single-walled carbon nanotubes and benzyne teeth should operate well at 50-100 gigahertz. Results suggest that rotation can be converted to rotating or linear motion, and linear motion may be converted into rotation. Preliminary results suggest that these mechanical systems can be cooled by a helium atmosphere. Furthermore, Deepak has successfully simulated using helical electric fields generated by a laser to power fullerene gears once a positive and negative charge have been added to form a dipole. Even with mechanical motion, cooling, and power; creating a viable nanotechnology requires support structures, computer control, a system architecture, a variety of components, and some approach to manufacture. Additional

  2. Lubrication of Machine Elements

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.

    1984-01-01

    The understanding of hydrodynamic lubrication began with the classical experiments of Tower and Petrov. Reynolds used a reduced form of the Navier-Stokes equations and the continuity equation to generate a second order differential equation for the pressure in the narrow, converging gap of a bearing contact. Such a pressure enables a load to be transmitted between the surfaces with very low friction since the surfaces are completely separated by a film of fluid. In such a situation it is the physical properties of the lubricant, notably the dynamic viscosity, that dictate the behavior of the contact. The understanding of boundary lubrication is normally attributed to Hardy and Doubleday. In boundary lubrication it is the physical and chemical properties of thin films of molecular proportions and the surfaces to which they are attached that determine contact behavior. The lubricant viscosity is not an influential parameter. Research is devoted to a better understanding and more precise definition of other lubrication regimes between these extremes. One such regime, elastohydrodynamic lubrication, occurs in nonconformal contacts, where the pressures are high and the bearing surfaces deform elastically. In this situation the viscosity of the lubricant may raise considerably, and this further assists the formation of an effective fluid film. The science of these three lubrication regimes (hydrodynamic, elastohydrodynamic, and boundary) are described and the manner in which this science is used in the design of machine elements is examined.

  3. Supramolecular polymers: Molecular machines muscle up

    NASA Astrophysics Data System (ADS)

    Bruns, Carson J.; Stoddart, J. Fraser

    2013-01-01

    A supramolecular polymer made of thousands of bistable [c2]daisy chains amplifies individual nanometric displacements up to the micrometre-length scale, in a concerted process reminiscent of muscular cells.

  4. Computational studies of molecular machines: the ribosome.

    PubMed

    Sanbonmatsu, Karissa Y

    2012-04-01

    The past decade has produced an avalanche of experimental data on the structure and dynamics of the ribosome. Groundbreaking studies in structural biology and kinetics have placed important constraints on ribosome structural dynamics. However, a gulf remains between static structures and time dependent data. In particular, X-ray crystallography and cryo-EM studies produce static models of the ribosome in various states, but lack dynamic information. Single molecule studies produce information on the rates of transitions between these states but do not have high-resolution spatial information. Computational studies have aided in bridging this gap by providing atomic resolution simulations of structural fluctuations and transitions between configurations. PMID:22336622

  5. Computational studies of molecular machines: the ribosome

    PubMed Central

    Sanbonmatsu, Karissa Y.

    2013-01-01

    The past decade has produced an avalanche of experimental data on the structure and dynamics of the ribosome. Groundbreaking studies in structural biology and kinetics have placed important constraints on ribosome structural dynamics. However, a gulf remains between static structures and time dependent data. In particular, x-ray crystallography and cryo-EM studies produce static models of the ribosome in various states, but lack dynamic information. Single molecule studies produce information on the rates of transitions between these states but do not have high-resolution spatial information. Computational studies have aided in bridging this gap by providing atomic resolution simulations of structural fluctuations and transitions between configurations. PMID:22336622

  6. Fault Tolerant State Machines

    NASA Technical Reports Server (NTRS)

    Burke, Gary R.; Taft, Stephanie

    2004-01-01

    State machines are commonly used to control sequential logic in FPGAs and ASKS. An errant state machine can cause considerable damage to the device it is controlling. For example in space applications, the FPGA might be controlling Pyros, which when fired at the wrong time will cause a mission failure. Even a well designed state machine can be subject to random errors us a result of SEUs from the radiation environment in space. There are various ways to encode the states of a state machine, and the type of encoding makes a large difference in the susceptibility of the state machine to radiation. In this paper we compare 4 methods of state machine encoding and find which method gives the best fault tolerance, as well as determining the resources needed for each method.

  7. Machine tool locator

    DOEpatents

    Hanlon, John A.; Gill, Timothy J.

    2001-01-01

    Machine tools can be accurately measured and positioned on manufacturing machines within very small tolerances by use of an autocollimator on a 3-axis mount on a manufacturing machine and positioned so as to focus on a reference tooling ball or a machine tool, a digital camera connected to the viewing end of the autocollimator, and a marker and measure generator for receiving digital images from the camera, then displaying or measuring distances between the projection reticle and the reference reticle on the monitoring screen, and relating the distances to the actual position of the autocollimator relative to the reference tooling ball. The images and measurements are used to set the position of the machine tool and to measure the size and shape of the machine tool tip, and examine cutting edge wear. patent

  8. Chaotic Boltzmann machines

    PubMed Central

    Suzuki, Hideyuki; Imura, Jun-ichi; Horio, Yoshihiko; Aihara, Kazuyuki

    2013-01-01

    The chaotic Boltzmann machine proposed in this paper is a chaotic pseudo-billiard system that works as a Boltzmann machine. Chaotic Boltzmann machines are shown numerically to have computing abilities comparable to conventional (stochastic) Boltzmann machines. Since no randomness is required, efficient hardware implementation is expected. Moreover, the ferromagnetic phase transition of the Ising model is shown to be characterised by the largest Lyapunov exponent of the proposed system. In general, a method to relate probabilistic models to nonlinear dynamics by derandomising Gibbs sampling is presented. PMID:23558425

  9. Applying Machine Vision To Robotic Automation

    NASA Astrophysics Data System (ADS)

    Lee, Jay

    1987-10-01

    Machine vision is an integral part in industry automation. This paper will discuss the 3-D vision technology and its applications. A brief description of several turkey automation systems developed and being developed that using 3-D vision technology in the fields of inspection and robotic guidance&control will be presented. The applications range from advanced robotic technology in automotive car production to sophisticated robotic system for U.S. Navy and Air force. This 3-D vision measuring capability has proved to the versatile key to successfully implementing adaptively controlled robot motion and robot path. Other extension of the technology to provide 3-D volumetric sensing and research effort in integrating 3-D vision with CAD/CAM system are examined.

  10. Virtual Machine Language 2.1

    NASA Technical Reports Server (NTRS)

    Riedel, Joseph E.; Grasso, Christopher A.

    2012-01-01

    VML (Virtual Machine Language) is an advanced computing environment that allows spacecraft to operate using mechanisms ranging from simple, time-oriented sequencing to advanced, multicomponent reactive systems. VML has developed in four evolutionary stages. VML 0 is a core execution capability providing multi-threaded command execution, integer data types, and rudimentary branching. VML 1 added named parameterized procedures, extensive polymorphism, data typing, branching, looping issuance of commands using run-time parameters, and named global variables. VML 2 added for loops, data verification, telemetry reaction, and an open flight adaptation architecture. VML 2.1 contains major advances in control flow capabilities for executable state machines. On the resource requirements front, VML 2.1 features a reduced memory footprint in order to fit more capability into modestly sized flight processors, and endian-neutral data access for compatibility with Intel little-endian processors. Sequence packaging has been improved with object-oriented programming constructs and the use of implicit (rather than explicit) time tags on statements. Sequence event detection has been significantly enhanced with multi-variable waiting, which allows a sequence to detect and react to conditions defined by complex expressions with multiple global variables. This multi-variable waiting serves as the basis for implementing parallel rule checking, which in turn, makes possible executable state machines. The new state machine feature in VML 2.1 allows the creation of sophisticated autonomous reactive systems without the need to develop expensive flight software. Users specify named states and transitions, along with the truth conditions required, before taking transitions. Transitions with the same signal name allow separate state machines to coordinate actions: the conditions distributed across all state machines necessary to arm a particular signal are evaluated, and once found true, that

  11. Diamond machine tool face lapping machine

    DOEpatents

    Yetter, H.H.

    1985-05-06

    An apparatus for shaping, sharpening and polishing diamond-tipped single-point machine tools. The isolation of a rotating grinding wheel from its driving apparatus using an air bearing and causing the tool to be shaped, polished or sharpened to be moved across the surface of the grinding wheel so that it does not remain at one radius for more than a single rotation of the grinding wheel has been found to readily result in machine tools of a quality which can only be obtained by the most tedious and costly processing procedures, and previously unattainable by simple lapping techniques.

  12. Flexible electronics: Sophisticated skin

    NASA Astrophysics Data System (ADS)

    Bauer, Siegfried

    2013-10-01

    Advances in materials science and layout design have enabled the realization of flexible and multifunctional electronic devices. Two demonstrations of electronic skins, which combine temperature and pressure sensing with integrated thermal actuators and organic displays, unveil the potential of these devices for robotics and clinical applications.

  13. Machine Translation Project

    NASA Technical Reports Server (NTRS)

    Bajis, Katie

    1993-01-01

    The characteristics and capabilities of existing machine translation systems were examined and procurement recommendations were developed. Four systems, SYSTRAN, GLOBALINK, PC TRANSLATOR, and STYLUS, were determined to meet the NASA requirements for a machine translation system. Initially, four language pairs were selected for implementation. These are Russian-English, French-English, German-English, and Japanese-English.

  14. Simple Machines Made Simple.

    ERIC Educational Resources Information Center

    St. Andre, Ralph E.

    Simple machines have become a lost point of study in elementary schools as teachers continue to have more material to cover. This manual provides hands-on, cooperative learning activities for grades three through eight concerning the six simple machines: wheel and axle, inclined plane, screw, pulley, wedge, and lever. Most activities can be…

  15. Simple Machine Junk Cars

    ERIC Educational Resources Information Center

    Herald, Christine

    2010-01-01

    During the month of May, the author's eighth-grade physical science students study the six simple machines through hands-on activities, reading assignments, videos, and notes. At the end of the month, they can easily identify the six types of simple machine: inclined plane, wheel and axle, pulley, screw, wedge, and lever. To conclude this unit,…

  16. Compound taper milling machine

    NASA Technical Reports Server (NTRS)

    Campbell, N. R.

    1969-01-01

    Simple, inexpensive milling machine tapers panels from a common apex to a uniform height at panel edge regardless of the panel perimeter configuration. The machine consists of an adjustable angled beam upon which the milling tool moves back and forth above a rotatable table upon which the workpiece is held.

  17. Technique for Machining Glass

    NASA Technical Reports Server (NTRS)

    Rice, S. H.

    1982-01-01

    Process for machining glass with conventional carbide tools requires a small quantity of a lubricant for aluminum applied to area of glass to be machined. A carbide tool is then placed against workpiece with light pressure. Tool is raised periodically to clear work of glass dust and particles. Additional lubricant is applied as it is displaced.

  18. THE TEACHING MACHINE.

    ERIC Educational Resources Information Center

    KLEIN, CHARLES; WAYNE, ELLIS

    THE ROLE OF THE TEACHING MACHINE IS COMPARED WITH THE ROLE OF THE PROGRAMED TEXTBOOK. THE TEACHING MACHINE IS USED FOR INDIVIDUAL INSTRUCTION, CONTAINS AND PRESENTS PROGRAM CONTENT IN STEPS, PROVIDES A MEANS WHEREBY THE STUDENT MAY RESPOND TO THE PROGRAM, PROVIDES THE STUDENT WITH IMMEDIATE INFORMATION OF SOME KIND CONCERNING HIS RESPONSE THAT CAN…

  19. Stirling machine operating experience

    SciTech Connect

    Ross, B.; Dudenhoefer, J.E.

    1994-09-01

    Numerous Stirling machines have been built and operated, but the operating experience of these machines is not well known. It is important to examine this operating experience in detail, because it largely substantiates the claim that stirling machines are capable of reliable and lengthy operating lives. The amount of data that exists is impressive, considering that many of the machines that have been built are developmental machines intended to show proof of concept, and are not expected to operate for lengthy periods of time. Some Stirling machines (typically free-piston machines) achieve long life through non-contact bearings, while other Stirling machines (typically kinematic) have achieved long operating lives through regular seal and bearing replacements. In addition to engine and system testing, life testing of critical components is also considered. The record in this paper is not complete, due to the reluctance of some organizations to release operational data and because several organizations were not contacted. The authors intend to repeat this assessment in three years, hoping for even greater participation.

  20. An asymptotical machine

    NASA Astrophysics Data System (ADS)

    Cristallini, Achille

    2016-07-01

    A new and intriguing machine may be obtained replacing the moving pulley of a gun tackle with a fixed point in the rope. Its most important feature is the asymptotic efficiency. Here we obtain a satisfactory description of this machine by means of vector calculus and elementary trigonometry. The mathematical model has been compared with experimental data and briefly discussed.

  1. Machining heavy plastic sections

    NASA Technical Reports Server (NTRS)

    Stalkup, O. M.

    1967-01-01

    Machining technique produces consistently satisfactory plane-parallel optical surfaces for pressure windows, made of plexiglass, required to support a photographic study of liquid rocket combustion processes. The surfaces are machined and polished to the required tolerances and show no degradation from stress relaxation over periods as long as 6 months.

  2. Friction-Testing Machine

    NASA Technical Reports Server (NTRS)

    Benz, F. J.; Dixon, D. S.; Shaw, R. C.

    1986-01-01

    Testing machine evaluates wear and ignition characteristics of materials in rubbing contact. Offers advantages over other laboratory methods of measuring wear because it simulates operating conditions under which material will actually be used. Machine used to determine wear characteristics, rank and select materials for service with such active oxidizers as oxygen, halogens, and oxides of nitrogen, measure wear characteristics, and determine coefficients of friction.

  3. BRITISH MOLDING MACHINE, PBQ AUTOMATIC COPE AND DRAG MOLDING MACHINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    BRITISH MOLDING MACHINE, PBQ AUTOMATIC COPE AND DRAG MOLDING MACHINE MAKES BOTH MOLD HALVES INDIVIDUALLY WHICH ARE LATER ROTATED, ASSEMBLED, AND LOWERED TO POURING CONVEYORS BY ASSISTING MACHINES. - Southern Ductile Casting Company, Casting, 2217 Carolina Avenue, Bessemer, Jefferson County, AL

  4. 14. Interior, Machine Shop, Roundhouse Machine Shop Extension, Southern Pacific ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Interior, Machine Shop, Roundhouse Machine Shop Extension, Southern Pacific Railroad Carlin Shops, view to north (90mm lens). - Southern Pacific Railroad, Carlin Shops, Roundhouse Machine Shop Extension, Foot of Sixth Street, Carlin, Elko County, NV

  5. Using Argument-Driven Inquiry to enhance students' argument sophistication when supporting a stance in the context of Socioscientific Issues

    NASA Astrophysics Data System (ADS)

    Grooms, Jonathon A.

    This quasi-experimental study assesses the extent to which the Argument-Driven Inquiry (ADI) instructional model enhances undergraduate students' abilities to generate quality arguments supporting their stance in the context of a Socioscientific Issue (SSI) as compared to students experiencing a traditional style of instruction. Enhancing the quality of undergraduate students' arguments in the context of SSI can serve as an indirect measure of their scientific literacy and their ability to make sound decisions on issues that are inherently scientific but also involve social implications. Data collected in this study suggest that the undergraduate students experiencing the ADI instruction more readily provide rationales in their arguments supporting their decisions regarding two SSI-tasks as compared to a group of undergraduate students experiencing traditional instruction. This improvement in argument quality and gain in scientific literacy was achieved despite the overall lower SSI related content knowledge of the ADI students. Furthermore, the gap between the argument quality of those students with high versus low SSI related content knowledge was closed within the ADI group, while the same gap persisted post-intervention within the traditional instruction students. The role of students' epistemological sophistication was also investigated, which showed that neither instructional strategy was effective at shifting students' epistemological sophistication toward an evaluativist stance. However, the multiplists within the ADI group were able to significantly increase the sophistication of their arguments whereas the traditional students were not. There were no differences between the quality of arguments generated by the evaluativist students with either the treatment or comparison groups. Finally, the nature of the justifications used by the students revealed that the students (both comparison and treatment groups) did not invoke science-based justifications when

  6. Machine tool evaluation and machining operation development

    SciTech Connect

    Morris, T.O.; Kegg, R.

    1997-03-15

    The purpose of this CRADA was to support Cincinnati Milacron`s needs in fabricating precision components, from difficult to machine materials, while maintaining and enhancing the precision manufacturing skills of the Oak Ridge Complex. Oak Ridge and Cincinnati Milacron personnel worked in a team relationship wherein each contributed equally to the success of the program. Process characterization, control technologies, machine tool capabilities, and environmental issues were the primary focus areas. In general, Oak Ridge contributed a wider range of expertise in machine tool testing and monitoring, and environmental testing on machining fluids to the defined tasks while Cincinnati Milacron personnel provided equipment, operations-specific knowledge and shop-floor services to each task. Cincinnati Milacron was very pleased with the results of all of the CRADA tasks. However, some of the environmental tasks were not carried through to a desired completion due to an expanding realization of need as the work progressed. This expansion of the desired goals then exceeded the time length of the CRADA. Discussions are underway on continuing these tasks under either a Work for Others agreement or some alternate funding.

  7. Micro-machining.

    PubMed

    Brinksmeier, Ekkard; Preuss, Werner

    2012-08-28

    Manipulating bulk material at the atomic level is considered to be the domain of physics, chemistry and nanotechnology. However, precision engineering, especially micro-machining, has become a powerful tool for controlling the surface properties and sub-surface integrity of the optical, electronic and mechanical functional parts in a regime where continuum mechanics is left behind and the quantum nature of matter comes into play. The surprising subtlety of micro-machining results from the extraordinary precision of tools, machines and controls expanding into the nanometre range-a hundred times more precise than the wavelength of light. In this paper, we will outline the development of precision engineering, highlight modern achievements of ultra-precision machining and discuss the necessity of a deeper physical understanding of micro-machining. PMID:22802498

  8. The basic anaesthesia machine.

    PubMed

    Gurudatt, Cl

    2013-09-01

    After WTG Morton's first public demonstration in 1846 of use of ether as an anaesthetic agent, for many years anaesthesiologists did not require a machine to deliver anaesthesia to the patients. After the introduction of oxygen and nitrous oxide in the form of compressed gases in cylinders, there was a necessity for mounting these cylinders on a metal frame. This stimulated many people to attempt to construct the anaesthesia machine. HEG Boyle in the year 1917 modified the Gwathmey's machine and this became popular as Boyle anaesthesia machine. Though a lot of changes have been made for the original Boyle machine still the basic structure remains the same. All the subsequent changes which have been brought are mainly to improve the safety of the patients. Knowing the details of the basic machine will make the trainee to understand the additional improvements. It is also important for every practicing anaesthesiologist to have a thorough knowledge of the basic anaesthesia machine for safe conduct of anaesthesia. PMID:24249876

  9. Machine Learning and Radiology

    PubMed Central

    Wang, Shijun; Summers, Ronald M.

    2012-01-01

    In this paper, we give a short introduction to machine learning and survey its applications in radiology. We focused on six categories of applications in radiology: medical image segmentation, registration, computer aided detection and diagnosis, brain function or activity analysis and neurological disease diagnosis from fMR images, content-based image retrieval systems for CT or MRI images, and text analysis of radiology reports using natural language processing (NLP) and natural language understanding (NLU). This survey shows that machine learning plays a key role in many radiology applications. Machine learning identifies complex patterns automatically and helps radiologists make intelligent decisions on radiology data such as conventional radiographs, CT, MRI, and PET images and radiology reports. In many applications, the performance of machine learning-based automatic detection and diagnosis systems has shown to be comparable to that of a well-trained and experienced radiologist. Technology development in machine learning and radiology will benefit from each other in the long run. Key contributions and common characteristics of machine learning techniques in radiology are discussed. We also discuss the problem of translating machine learning applications to the radiology clinical setting, including advantages and potential barriers. PMID:22465077

  10. The Basic Anaesthesia Machine

    PubMed Central

    Gurudatt, CL

    2013-01-01

    After WTG Morton's first public demonstration in 1846 of use of ether as an anaesthetic agent, for many years anaesthesiologists did not require a machine to deliver anaesthesia to the patients. After the introduction of oxygen and nitrous oxide in the form of compressed gases in cylinders, there was a necessity for mounting these cylinders on a metal frame. This stimulated many people to attempt to construct the anaesthesia machine. HEG Boyle in the year 1917 modified the Gwathmey's machine and this became popular as Boyle anaesthesia machine. Though a lot of changes have been made for the original Boyle machine still the basic structure remains the same. All the subsequent changes which have been brought are mainly to improve the safety of the patients. Knowing the details of the basic machine will make the trainee to understand the additional improvements. It is also important for every practicing anaesthesiologist to have a thorough knowledge of the basic anaesthesia machine for safe conduct of anaesthesia. PMID:24249876